Colorectal cancer constitutes a major health problem for elderly patients. The disease and its stage, treatment, and attendant symptoms can have significant negative impact on the mental functioning of these patients. As part of a larger longitudinal study, 158 patients 65 years of age or older with an incident diagnosis of colorectal cancer were recruited from 23 sites within a Midwestern state. Random effects regression analysis techniques were used to analyze how age, gender, race, presence of a family caregiver, co-morbid conditions, stage of disease at diagnosis, and the time-dependent variables marital status, employment status, symptoms, physical functioning, social functioning, and treatment predict depressive symptomatology at four assessments over the 1st year following diagnosis. Gender, race, co-morbid conditions, physical functioning, social functioning, and symptoms were significant predictors of depressive symptomatology over the four waves of the study. Female patients, African Americans, and patients with two or more co-morbid conditions exhibited more depressive symptomatology. Both more symptoms and more restricted physical and social functioning corresponded to higher levels of depressive symptomatology. At a clinical level of patient care, these findings mandate early identification of psychosocial difficulties experienced, an individualized symptom management plan and the application of other interventions, such as information giving, reassurance and referral to other resources, with particular attention to African American and female patients.