Eccrine spiradenoma (ES) is a rare, benign adnexal neoplasm that may easily be mistaken for glomus lesions or angioleiomyoma due to its painfulness and florid vascularization. A 44-year-old male with a blue-colored, nodular tumor on the left knee, present for 10 years, was submitted for diagnosis. Dermatological examination was undertaken, followed by surgical excision of the subcutaneous lesion and histopathological examination of the tissue. Subjective symptoms included tenderness upon palpation and routine investigations were within normal limits. Immunohistochemical analysis of the tumor cells demonstrated positive staining for CK5/CK6, CK8/CK18, S100, as well as small vacuole-like positive for EMA, and was therefore diagnosed as ES. The results of the present study suggest that immunohistochemical assays may be helpful to clarify the diagnosis and differentiate ES from other painful subcutaneous tumors exhibiting similar clinical and histological presentations.