Melanoma may arise in association with and/or simulate the appearance of a cellular blue nevus. The distinction of a cellular blue nevus with atypical features from blue nevus-like melanoma can be difficult. One rare setting, in which one may face this diagnostic challenge, is nodule formation in a large plaque-type blue nevus. We have previously reported 2 patients with cellular blue nevus-like subcutaneous nodules without overt malignant features and indolent clinical behavior. Herein we report a patient who developed malignant melanoma in association with a large plaque-type blue nevus. A 46-year-old woman with a history of "cellular blue nevus" of the breast that developed 7 years earlier during pregnancy had soft tissue nodules at the prior surgical site. She was found to have melanoma associated with a large plaque-type blue nevus, which involved the skin and subcutis of the chest wall and extended into breast parenchyma. Ten years after mastectomy and axillary node dissection with negative lymph nodes, the melanoma recurred as a subcutaneous chest wall nodule. Cytogenetic analysis revealed a number of aberrations, including deletion of 6q and gains of 6p and 8q. The patient then developed visceral metastases, first to the liver, and died of widely metastatic melanoma. In contrast, the cytogenetic findings of a previously reported cellular blue nevus-like nodule in a patient with a large plaque-type blue nevus were normal. That patient is still alive with no evidence of melanoma 16 years after the surgical excision of the subcutaneous cellular blue nevus-like nodule.