Purpose To address gaps in evidence on the risk of cancer in people from sexual minorities. Patients and Methods We used data from 796,594 population-based English General Practice Patient Survey responders to explore the prevalence of self-reported diagnoses of cancer in the last 5 years among sexual minorities compared with heterosexual women and men. We analyzed data from 249,010 hospital-based English Cancer Patient Experience Survey responders with sexual orientation as a binary outcome, and International Classification of Diseases, Tenth, Revision, diagnosis as covariate-38 different common and rarer cancers, with breast and prostate cancer as baseline categories for women and men, respectively-to examine whether people from sexual minorities are over- or under-represented among different cancer sites. For both analyses, we used logistic regression, stratified by sex and adjusted for age. Results A diagnosis of cancer in the past 5 years was more commonly reported by male General Practice Patient Survey responders who endorsed gay or bisexual orientation compared with heterosexual men (odds ratio [OR], 1.31; 95% CI, 1.15 to 1.49; P < .001) without evidence of a difference between lesbian or bisexual compared with heterosexual women (OR, 1.14; 95% CI, 0.94 to 1.37; P = .19). For most common and rarer cancer sites (30 of 33 in women, 28 of 32 in men), the odds of specific cancer site diagnosis among Cancer Patient Experience Survey respondents seemed to be independent of sexual orientation; however, there were notable differences in infection-related (HIV and human papillomavirus [HPV]) cancers. Gay or bisexual men were over-represented among men with Kaposi's sarcoma (OR, 48.2; 95% CI, 22.0 to 105.6), anal (OR, 15.5; 95% CI, 11.0 to 21.9), and penile cancer (OR, 1.8; 95% CI, 0.9 to 3.7). Lesbian or bisexual women were over-represented among women with oropharyngeal cancer (OR, 3.2; 95% CI, 1.7 to 6.0). Conclusion Large-scale evidence indicates that the distribution of cancer sites does not vary substantially by sexual orientation, with the exception of some HPV- and HIV-associated cancers. These findings highlight the importance of HPV vaccination in heterosexual and sexual minority populations.