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 &OV0456;vwere 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 &OV0456;v,. was only moderate (r= .60). Euploid lesions had a smaller nuclear &OV0456;vthan 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 &OV0456;vand 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 &OV0456;vwas 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.