Purpose: The purpose of this study was to determine the independent and combined effects of cardiorespiratory fitness and obesity on all-cause cancer mortality for women and men. Methods: Using the Lipids Research Clinics Prevalence Study, we examined the relationship of fitness and obesity on cancer mortality among 2585 women and 2890 men followed from 1972-1976 to 1998. Cardiorespiratory fitness was measured using a treadmill test and obesity was assessed using body mass index (BMI) calculated from measured height and weight. Gender-specific hazard ratios (HR) were calculated from proportional hazard models, which included covariates for age, education, smoking, alcohol intake, Keys score, and menopause (women only). Results: Adjusted cancer mortality was significantly lower in the most fit quintile relative to the other four quintiles for men (HR = 0.47; 95% CI, 0.27-0.81) but not for women (HR = 0.84; 95% CI, 0.52-1.36). Adjusted cancer mortality was significantly higher in the highest BMI quintile relative to the other four BMI quintiles for women (HR = 1.49; 95% CI, 1.06-2.09) but not for men (HR = 1.05; 95% CI, 0.77-1.43). Further adjustment for BMI on fitness and adjustment for fitness on BMI did not meaningfully change the HR. There were no significant interactions between fitness and obesity in predicting cancer mortality for either women or men. Conclusion: In this study, high fitness was a stronger predictor of cancer mortality in men, whereas high BMI was a stronger predictor of cancer mortality in women.