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Context.—Spindle cell lipoma (SCL) is a tumor with marked male predilection. We discovered one SCL that exhibited strong immunoreactivity for androgen receptors (ARs) in the spindle cells. Objective.—The hypothesis was that ARs in SCLs would not be rare and that all or nearly all SCLs would be AR positive, perhaps explaining its male predominance. Design.—Twenty-eight cases of SCL (22 men, 6 women) and a control group of 20 conventional lipomas (10 men, 10 women) were stained with monoclonal AR antibody (1: 150; Dako, Carpinteria, Calif) using the Ventana Discovery. Only nuclear reactivity was considered positive, as noted in prostate controls. Cell types (fat, spindle cells) and extent of staining were recorded as rare, considered negative, focal (1+), or diffuse (2+/3+). Results.—All 22 cases of SCL in men were positive for ARs. Twenty showed diffuse (2+/3+) reactivity mainly in the spindle cells. Of the 6 SCLs in women, 1 was AR negative, 1 showed a 3+ reaction in the spindle cells, and 4 had weak (1+) staining of spindle cells. Overall, 96% of SCLs were AR positive, including 83% of SCLs in women. Seventy percent of conventional lipomas showed positive staining in fat, but only 2 showed 2+ staining. In the rest, staining was rare or weak (1+). Conclusions.—Nearly all SCLs exhibited AR reactivity. However, the presence of ARs in a substantial percentage of ordinary lipomas and in SCLs in females mitigates against the hypothesis that AR reactivity alone can explain the marked male predominance of SCL.