Abstract: Homogeneous staining regions (HSRs) have been previously shown to confer a worse prognosis in solid tumors and myelodysplastic syndromes. We previously reported a single case of melanoma with HSR for cyclin D1 and postulated that HSR for cyclin D1 is an independent poor prognostic indicator. Herein, we report 7 cases of melanoma with HSR for cyclin D1. The cases occurred in elderly men and women with an average age of 65 years. Three cases occurred in areas of intermittent sun exposure, 2 cases occurred in chronically sun-damaged areas, and 2 cases were acral. HSR correlated with aggressive histology. The average Breslow depth was 2.7 mm (range, 1–11 mm), the average mitotic index was 5.1 per square millimeter, and 5 of the 7 cases were ulcerated. Clinical follow-up was available for 6 of the 7 cases. Five of the 6 cases for which clinical follow-up was available metastasized, and 1 patient died of metastatic melanoma. Three cases with metastatic disease occurred in primary melanomas with lower Breslow depths, ranging from 1.0 to 1.4 mm. These additional cases of melanoma with an aggressive clinical course provide further evidence of the prognostic significance of HSR for cyclin D1 in melanoma. Larger cohort studies are needed to validate this observation.