The study’s purpose was to describe the relations among self-esteem, learned resourcefulness, and social support, and to show how they predict health-related quality of life (HRQL) for long-term survivors of cancer. With advances in oncology and increased survival, variables influencing the HRQL of long-term survivors of cancer must be explored. The design was descriptive and correlational. Five instruments were sent to 456 long-term survivors in southern California. Data were analyzed for 62 of 111 consenting individuals, most of whom were married, retired, white, college-educated, female survivors of breast cancer older than 60 years of age treated by radiation and surgery. Subjects with higher self-esteem reported higher HRQL (r= 0.69;p= 0.00). Learned resourcefulness had a significant negative relation with HRQL (r= −0.32;p= 0.01). Social support was operationalized as functional components, network properties, and recent loss. Only the loss component of social support had a significant negative relation with HRQL (r= −0.38;p= 0.00). Together, the three variables explained more than half of the variance (R2= 0.53) of HRQL, with self-esteem being the strongest predictor. The HRQL of long-term survivors of cancer may increase with interventions such as both survivor-and nurse-led support groups aimed at supporting and improving self-esteem. In addition, education to anticipate social support losses may further enhance HRQL.