Most previously employed cancer survivors continue to work after treatment, but the impact of cancer symptoms or psychosocial concerns on their work has seldom been assessed. We conducted a community-based survey of cancer survivors from the Colorado Central Cancer Registry to assess the changes in their work and the demographic, clinical, and psychosocial characteristics associated with work changes over the 2 years following diagnosis. Of 100 survivors, 92 returned to work, but 57% of those reduced their work by more than 4 h/week, and 56% noted a change in some aspect of their occupational role. Physical symptoms, particularly lack of energy or nausea/vomiting, and psychological symptoms, particularly feeling bored or useless or feeling depressed, were significantly associated with a reduction in work hours or a change in occupational role. Since changes in work are common and are associated with both physical and psychosocial symptoms, strategies are needed to reduce symptom burden and barriers to work and to improve work capacity for working-age cancer survivors.