Spiradenocarcinoma is a rare skin adnexal neoplasm with potential for aggressive behavior, classified histologically into low- and high-grade tumors. Morphologically, low-grade tumors are thought to behave more favorably. Limited information is available, however, with only 18 published cases. To study their clinical behavior, histological features, and the diagnostic value of immunohistochemistry, 19 morphologically low-grade spiradenocarcinomas were retrieved and compared with 21 spiradenomas and cylindromas. H&E-stained sections were reviewed, follow-up was obtained, and immunohistochemistry for Ki-67, p53 and, MYB was performed. The tumors were solitary, measuring 0.8-7 cm (median: 2.7 cm), with a predilection for the head and neck of elderly patients (median age: 72 years; range 53-92) without gender bias. Histologically, the tumors were multinodular and located in deep dermis and subcutis. A pre-existing spiradenoma was present in all cases. The malignant component was characterized by expansile growth with loss of the dual cell population, up to moderate cytological atypia and increased mitotic activity (median: 10/10 HPF; range 1-28). Additional findings included squamoid differentiation (n=9), necrosis (n=7), and ulceration (n=5). P53 expression was variable and no significant differences were noted in the benign compared with the malignant parts of the tumors. In contrast, in the malignant components the Ki-67 proliferative index was slightly increased, and MYB expression was lost. Follow-up (median: 67 months; range: 13-132) available for 16 patients (84%) revealed a local recurrence rate of 19% but no metastases or disease-related mortality. In this large study with long-term follow-up, we demonstrate that spiradenocarcinomas with low-grade morphology pursue an indolent course, characterized by local recurrence only. Metastases and disease-related mortality appear to be exceptional. Lack of MYB expression may be useful as an additional aid in the diagnosis of these challenging tumors.