Healthy lifestyle behaviors can improve health-related quality of life (HRQOL) in cancer survivors; but the combination of behaviors most important for HRQOL is not known. This study investigated the patterns of lifestyle behaviors among cancer survivors and differences in HRQOL between behavioral classes. Cancer survivors (n = 2,463) were invited to participate in a cross-sectional survey. Participants (N= 591) were predominately female (63%) and non-Hispanic White (90%). Survey items included self-reported physical activity, diet, smoking, sleep, HRQOL, and demographics. Behavioral classes were estimated by latent class analysis. Differences between classes were assessed by latent class regression. Compared with the "healthy lifestyles" class (higher probabilities of meeting aerobic/strength-based activity guidelines, high fruit/vegetable intake, and no sleep problems; 11% of sample), the "sleep and diet problems with inconsistent physical activity" class (higher probabilities of not meeting strength-based guidelines, low fruit/vegetable intake, some sleep problems; marginally higher probability of meeting aerobic guidelines; 41%) had poorer general and physical HRQOL. The "poor physical activity and diet" class (higher probabilities of not meeting aerobic/strength-based guidelines, low fruit/vegetable intake, and some sleep problems; 48%) had poorer general, physical, and mental HRQOL. Few participants exhibited healthy lifestyle patterns associated with HRQOL. The findings provide opportunities to develop differentiated multiple behavior-change interventions, targeted to two common patterns of behavior. A large subgroup of cancer survivors was susceptible to suboptimal physical activity and diet, warranting interventions exclusively targeting these behaviors. Another subgroup was susceptible to suboptimal physical activity, diet, and sleep, indicating interventions for this group should include strategies targeting these three behaviors.