To identify trends in a residual category of cancers not typically associated with tobacco, screening, or human immunodeficiency virus (HIV) infection. For persons aged 20-84, we used sex- and race-specific age-period-cohort (APC) models to describe temporal patterns of incidence (1975-2004) and mortality (1970-2004) in the U.S. for a residual cancer category that excluded non-Hodgkin lymphoma, Kaposi sarcoma, and cancer of the oral cavity and pharynx, esophagus, pancreas, larynx, lung and bronchus, urinary bladder, kidney and renal pelvis, colon and rectum, prostate, female breast, and cervix uteri. Age-specific incidence rose (0.1-0.9% per year, on average) in every sex-race group, with factors related to both time period and birth cohort membership appearing to accelerate the increases in women. Age-specific mortality fell (0.6-0.9% per year, on average) for black and white men and women, with the declines decelerating in white women but accelerating in the other sex-race groups. Extrapolations of APC models predicted higher age-adjusted incidence rates in white women (11%), black women (5%), and white men (4%) in 2005-2009, relative to 2000-2004, and lower rates in black men (-3%), accompanied by lower age-adjusted mortality rates in every sex-race group (-8% in black men, -3% in black women, -1% in white men, and -1% in white women). The possibility that increased incidence in women over time reflects changes in underlying risks, diagnostic practices, or better case ascertainment should be actively explored. Declining mortality may signify improvements in cancer care.