A 53-year-old man came with pain and swelling of the right upper third arm following heaviness while lifting weight for 3 months. The pain was sudden in onset, dull aching, radiating to the scapular aspect without any aggravating or relieving factors. The swelling appeared to be a lemon-sized one which gradually progressed in the last past 3 months. The patient had associated paraesthesia, numbness, and restricted mobility of the shoulder. The patient reported a history of significant weight loss and appetite. There was no history of inciting trauma or irradiation in the past. On examination, a diffuse swelling was noted in the right shoulder and right scapular aspect measuring approximately 15 cm ×x 10 cm ×x 7 cms. Swelling showed varied consistency with ill-defined borders & and margins. The skin over the swelling was stretched and shiny with dilated engorged veins over it. No bruit was felt over the swelling. The metabolic profile revealed a 10ten-fold rise in serum alkaline phosphatase and significant elevation of lactate dehydrogenase. Plain radiograph of the right shoulder with humerus revealed a large expansile lytic soft- tissue mass in the right proximal humerus involving both cortex and medulla with a wide zone of transition without sclerotic margins (as shown in, ). Non-enhanced computed tomography (CT) NECT scan of the right shoulder (coronal and axial sections) revealed a large expansile lytic soft- tissue density mass lesion measuring 10.8 cm × 7.8 cm × 9.2 cms at right upper 1/3rd of the humerus and showing loss of fat planes with right subscapularis, supraspinatus, and abutting right deltoid and pectoralis major muscle (as shown in, ). Magnetic resonance imaging (MRI) showed T1 hypointense, T2/PDFS hyperintense large well defined expansile lytic lesion measuring 10.8 cm × 7.9 cm × 9.2 cms with multi-loculated cysts and multiple blood-fluid levels involving right proximal humerus infiltrating right subscapularis and supraspinatus muscle with hyperintensities in infraspinatus and teres minor muscles (as shown in - to ). Tc-99m methylene diphosphonate (MDP) bone scan revealed abnormal tracer uptake in the right upper 1/3rd of humerus and scapula. No metastatic lesions were demonstrated with fluorine-18-fluorodeoxyglucose positron emission tomography (PET) imaging. The radiological evidence with the clustering of multifocal lesions in a single anatomic region throws a high index of suspicion towards osseous vascular tumors. It is highly questionable to differentiate between angiosarcoma, hemangioendothelioma, and hemangiopericytoma. Angiosarcoma may be more destructive, but cellular differentiation is not reliable. The possible differential diagnosis was bone marrow metastases, multiple myeloma, osseous angiosarcoma, osseous hemangioendothelioma, and osseous hemangiopericytoma. With the suspicion of a malignant tumor, the patient was subjected to an incisional biopsy. Grossly, the tumourigenic tissue was friable, tan red, and hemorrhagic with few areas of necrosis. Histopathologically, the tumor showed cytologically malignant cells that were epithelioid in appearance. The nuclei were vesicular and contain one or two small nucleoli and occasional macronuclei. The cytoplasm was scant to moderate, deeply eosinophilic, hold intact, and fragmented erythrocytes. Areas of vasoformation were also seen along with numerous mitotic figures. The tumor cells were arranged in solid sheets and also line the irregular vascular lumina. Along with extravasated erythrocytes scattered deposits of hemosiderin were present. A variable inflammatory infiltrates consisting of lymphocytes and neutrophils were also seen (as shown in ). Immunohistochemical analysis demonstrated von Willebrand factor, Vimentin, CD-31 (as shown in ) and -34, factor 8 RA positivity which confirmed the tumor of vascular origin, and hence a confirmed diagnosis of primary angiosarcoma of osseous origin (humerus) was made. Our patient was treated with 6 cycles (one cycle per /month) of palliative chemotherapeutic agents according to mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) protocol (mesna, doxorubicin, ifosfamide, and dacarbazine) and was followed up for 6 months after the last cycle of chemotherapy. The patient presented with a decreased in the size of the mass with decreased pain over the right humerus at the end of 1 year. The patient was still under follow-up.