A low second-to-fourth digit ratio (2D:4D) is a purported biomarker of increased intrauterine androgenic exposure, presumably linked to postnatal behavior. We aimed to examine the associations between 2D:4D and adolescence behavior problems expected from high (externalizing and attention problems) or low (internalizing problems) prenatal androgen exposure. We conducted a cross-sectional study of 1042 Colombian schoolchildren aged 11–18 y. We examined whether caliper-assessed 2D:4D was associated with behavior problems per the Youth Self-Report questionnaire. Mean problem standardized score point differences were estimated between hand- and sex-specific quintiles of 2D:4D with use of multivariable linear regression. Lower right-hand 2D:4D was associated with decreased externalizing and internalizing behavior problem scores. Corresponding lowest-to-median quintile adjusted mean differences (95% CI) were −4.6 (−7.5, −1.7) and −3.5 (−6.4, −0.6) points in boys; and −3.4 (−5.9, −0.9) and −3.5 (−6.2, −0.8) points in girls. Lower right-hand 2D:4D was also related to less attention and thought problems in boys, and to less social problems among girls. Associations were nonlinear, apparent only below 2D:4D medians, and stronger with the right than the left hand. In conclusion, right-hand 2D:4D is related to behavior problems in adolescence in directions that are not fully consistent with an androgenic exposure origin.