12075 Background: Few studies have investigated long-term survival and causes of death among men and women diagnosed with major cancers. Methods: We estimated overall and cause-specific mortality rates for men diagnosed with prostate, lung and bronchus, colon and rectum, bladder, and melanoma cancer in the Health Professionals Follow-up Study between 1986-2010+, and women with breast, lung and bronchus, colon and rectum, uterine corpus, thyroid, and ovarian cancer in the Nurses’ Health Study (NHS) between 1976-2010+ and NHS II between 1989-2010+. Kaplan-Meier curves were used to calculate cumulative mortality rates at 5, 10, 15, 20, and 30 years and competing risk methods were used to calculate cumulative cancer-specific mortality rates of major causes at 5, 10, 15, 20, and 30 years. Additionally, among women 40-year mortality rates were calculated. Results: Except for lung and ovarian, most major cancer patients are more likely to die from other causes than the index cancer. We observed two basic patterns for cumulative cancer-specific mortality rates. The first pattern is greatly diminished risk of index cancer-specific mortality 10 years or more following diagnosis - for colorectal cancer, cancer-specific mortality rate increased by less than 3% between 10 to 30- or 40-year following diagnosis (among men, from 35.1% to 36.7%; among women, from 34.8% to 37.7%), and this pattern also applied to bladder, melanoma, or uterine corpus cancer. The second one is sustained, but nevertheless low, excess risk - prostate cancer-specific mortality rate increased gradually and almost linearly from 5.3% to 15.1% after diagnosis from 5 to 30 years, and for breast cancer, it increased likewise from 7.2% to 18.9% after diagnosis from 5 to 40 years. Conclusions: Except for lung and ovarian cancers, patients diagnosed with major cancers were more likely to die from causes other than cancer. Colorectal, bladder, melanoma or uterine corpus cancer patients surviving more than 10 years after diagnosis are unlikely to ever die from that disease. [Table: see text]