Background:Night shift work, exposure to light at night (ALAN) and circadian disruption may increase the risk of hormone-dependent cancers.Objectives:We evaluated the association of exposure to ALAN during sleeping time with breast and prostate cancer in a population based multicase–control study (MCC-Spain), among subjects who had never worked at night. We evaluated chronotype, a characteristic that may relate to adaptation to light at night.Methods:We enrolled 1,219 breast cancer cases, 1,385 female controls, 623 prostate cancer cases, and 879 male controls from 11 Spanish regions in 2008–2013. Indoor ALAN information was obtained through questionnaires. Outdoor ALAN was analyzed using images from the International Space Station (ISS) available for Barcelona and Madrid for 2012–2013, including data of remotely sensed upward light intensity and blue light spectrum information for each geocoded longest residence of each MCC-Spain subject.Results:Among Barcelona and Madrid participants with information on both indoor and outdoor ALAN, exposure to outdoor ALAN in the blue light spectrum was associated with breast cancer [adjusted odds ratio (OR) for highest vs. lowest tertile, ; 95% CI: 1.00, 2.17] and prostate cancer (; 95% CI: 1.38, 3.03). In contrast, those exposed to the highest versus lowest intensity of outdoor ALAN were more likely to be controls than cases, particularly for prostate cancer. Compared with those who reported sleeping in total darkness, men who slept in “quite illuminated” bedrooms had a higher risk of prostate cancer (; 95% CI: 1.55, 5.04), whereas women had a slightly lower risk of breast cancer (; 95% CI: 0.39, 1.51).Conclusion:Both prostate and breast cancer were associated with high estimated exposure to outdoor ALAN in the blue-enriched light spectrum. https://doi.org/10.1289/EHP1837