Background: The role of personality in the causation of cancer has been controversial. We examined this question in a large, prospective study. Methods: From June through August 1990, 30 277 residents of Miyagi Prefecture in northern Japan completed a Japanese version of the short form of the Eysenck Personality Questionnaire-Revised and a questionnaire on various health habits. There were 671 prevalent cases of cancer at baseline, and 986 incident cases of cancer were identified during 7 years of follow-up, through December 1997. We used Cox proportional hazards regression to estimate the relative risk (RR) of incident cancer (total, stomach, colorectal, breast, and lung) according to four levels of each of four personality subscales (extraversion, neuroticism, psychoticism, and lie), with adjustment for sex, age, education, smoking, alcohol use, body mass index, and family history of cancer. Statistical tests were two-sided. Results: Multivariable RRs of total cancer for individuals in the highest level of each personality subscale as compared with those in the lowest were 0.9 for extraversion (95% confidence interval [CI] = 0.7 to 1.1; Ptrend = .32), 1.1 for psychoticism (95% CI = 0.9 to 1.3; Ptrend = .96), 0.9 for lie (95% CI = 0.7 to 1.0; Ptrend = .19), and 1.2 for neuroticism (95% CI = 1.0 to 1.4; Ptrend = .06). There were no associations between any personality subscale and risk of specific cancers. Neuroticism showed statistically significant positive, linear associations with prevalent cancer at baseline (Ptrend<.001) and with the 320 incident cancer cases diagnosed within the first 3 years of follow-up (Ptrend = .03); however, it showed no association with the 666 cases diagnosed during the fourth through the seventh years of follow-up (Ptrend = .43). Conclusion: Our data do not support the hypothesis that personality is a risk factor for cancer incidence. The association between neuroticism and prevalent cancer may be a consequence, rather than a cause, of cancer diagnosis or symptoms.