The features most frequently used in predicting the outcome of renal cell carcinoma are stage at presentation and nuclear grade. Recently DNA ploidy pattern, as detected by DNA flow cytometry has also been shown to be predictive. In this study DNA flow cytometry was performed on formalin-fixed paraffin-embedded tissue from 50 patients with Stage I renal cell carcinoma for whom long-term follow-up data were available. Two were eliminated for technical reasons. Of the 48 evaluable tumors, 25 (52%) were diploid, 19 (40%) were nondiploid, and in four, (8%) the ploidy was uncertain. The ploidy pattern was statistically significantly associated with nuclear grade (P less than 0.02), and primary tumor size (P less than 0.05) but did not correlate with cell type, microscopic growth pattern, or the presence or absence of mitotic activity. In the group as a whole, ten patients (21%) died of renal cell carcinoma, seven of 19 (37%) with nondiploid tumor patterns, and two of 25 (8%) with a diploid pattern (P less than 0.03). One of four patients (25%) with tumors of uncertain ploidy also died. However, only two factors, nuclear grade and primary tumor size, were independent predictors of outcome. For Stage I renal cell carcinoma, ploidy can significantly predict patient outcome and correlates with nuclear grade and tumor size, but is not an independent predictive variable.