We describe the case of a 42-year-old Caucasian man who was diagnosed with BC in 1993. The patient reported a case of BC in his family, anyway without a medical history of risk factors for BC. In June 1993, he underwent to a radical mastectomy with axillary lymphadenectomy; histopathological examination confirmed infiltrating ductal carcinoma of the right breast with poor cellular differentiation, G3, large areas of necrosis, infiltration of subcutaneous tissue and muscular involvement. Biological characterization was not available. The final pathologic stage was pT4pN0(0/12)M0. He was given adjuvant treatment with six cycles of CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, fluorouracil 600 mg/m2) administered day 1–8, every 4 weeks, endocrine therapy with tamoxifen 20 mg daily for 5 years and complementary radiotherapy on the chest wall. In May 1996, during follow-up, a computed tomography (CT) scan revealed multiple lung metastases. Hereafter the patient started a first-line weekly paclitaxel chemotherapy, obtaining a partial response. In March 1997, paclitaxel was stopped because of lung metastases progression and an endocrine therapy with megestrol was administered until January 2000 when it was discontinued for a vein thrombosis and switch to exemestane. In January 2001, a new CT showed a further progression of disease (PD). Epirubicin and docetaxel were administered until June 2001 when a further lung progression was revealed. Thus, patient was given letrozole, 2.5 mg daily, until January 2002 when his lung disease progressed. A course of vinorelbine was started but in December 2002 chemotherapy was interrupted for PD and a re-challenge with megestrol produced a partial response until October 2007 when disease progressed again. We performed a lung biopsy to confirm etiology and histological examination was positive for BC metastases, immunohistochemistry showed positive staining for the estrogen receptor (ER) 99%, negative for progesterone receptor (PR) 0, 1% and for herceptest (1+). Ki67 was 21%. In October 2007, a re-challenge was done with tamoxifen, previously used in the adjuvant setting, and in May 2008, with a stable disease and a poor compliance, it was suspended. In January 2009, lung metastases progressed and capecitabine was prescribed observing stable disease for 2 years. From February 2011 until March 2013, a metronomic combination of cyclophosphamide and methotrexate was administered. In April 2013, bone and nodes metastases were diagnosed, then he received bone palliative radiotherapy. In May 2013 carboplatin and zoledronic acid were given, but a progressive disease was observed in October 2013 (lung, subcutaneous metastases). A biopsy of skin lesions confirmed breast cancer metastases. We commenced eribuline for a total of six cycles with no clinical benefit. Consequently, we interrupted therapy for PD with pulmonary lymphangitis, pulmonary thromboembolism and significant deterioration of the patient’s clinical condition (Eastern Cooperative Oncology Group Performance Status, ECOG PS 2). In May 2014 an off-label treatment with everolimus (EVE) and exemestane (EXE) was requested and approved by Ethics Committee of the Marche Region (CERM). After one month of treatment with everolimus, it was possible to highlight the complete response of the skin lesions had almost completely disappeared and were no longer palpable on physical examination. Whereas, a partial response of the other skin lesions located in the right mammary region is evident. At the start of the combined treatment, there were ulcerative lesions which healed. Unfortunately, this treatment lasted for 4 months only due to the deterioration of the patient’s clinical condition. Dyspnea was, in fact, evident, at the start of the fifth cycle. The patient complained of coughing and further worsening of his ECOG PS. A chest radiography was done which was strongly suggestive of pneumonitis then we interrupted treatment with everolimus and exemestane and we started him on systemic steroid therapy, bronchodilators and supplemental oxygen. A new X-ray was done 10 days after cessation of treatment and highlights an improvement in the pneumonitis. Despite this improvement in his breathing symptoms, his clinical condition worsened. He became even more cachectic and sadly expired a month later. Table resumed patient’s medical history. In 1996, the patient underwent genetic counseling and genetic testing which was negative for BRCA1 and BRCA2 gene mutation.