Large plaque-type blue nevi with subcutaneous cellular nodules are rare tumors occurring on the trunk with deep extension into underlying soft tissues. The histopathologic appearance consists of deep nodules resembling cellular blue nevi with interspersed foci of common blue nevus. Conservative management has been recommended, and metastases have not been observed. This report discusses two cases with microscopic features of large plaque-type blue nevi with subcutaneous cellular nodules in which comparative genomic hybridization showed chromosomal aberrations typical of melanoma. In both cases, the nodules showed gains involving chromosome 6p and losses involving chromosome 6q, which are among the most commonly found aberrations in melanoma. These copy number changes were not present in the less cellular surrounding areas that appeared characteristic of blue nevus. These cases illustrate that large blue nevi with a deep, multi-nodular configuration should be interpreted with caution, and that superficial biopsies of such lesions can be misleading. Molecular techniques can provide valuable insights in these types of difficult melanocytic neoplasms.