The mutual relation and prognostic value of three quantitative variables were investigated in a retrospective series of 56 stage I cutaneous malignant melanomas. Unbiased stereological estimates of nuclear volume, nuclear nu v were obtained along with measurements of melanoma thickness. The DNA index (DI) was determined by flow cytometry in adjacent sections from the same paraffin-embedded specimens. The correlation between tumor thickness and nuclear nu v was only moderate (r = .60). Euploid lesions had a smaller nuclear nu v than aneuploid tumors (2p = .01), but with considerable overlap. No significant association between tumor thickness and DI could be demonstrated. Single-factor analysis showed prognostic value of nuclear nu v and tumor thickness (2p = .0007 and 2p = .03, respectively), whereas DI was without prognostic impact (2p = .54). When analyzing the three parameters in a Cox model, nuclear nu v was the only independent, prognostically significant variable. Physical, three-dimensional nuclear volume is not solely a reflection of nuclear DNA content, and may represent a valuable, quantitative prognostic indicator in cutaneous malignant melanomas.