The objectives of this study were twofold: (1) to explore and compare the symptom experience of seriously ill hospitalized cancer and noncancer patients near the end of life using the Memorial Symptom Assessment Scale (MSAS) and (2) to determine if the MSAS is a valid and useful measure of symptom distress for patients with noncancer conditions. This was a prospective cohort study of hospitalized patients with end-stage congestive heart disease, chronic pulmonary disease, cirrhosis, or metastatic cancer. Eligible patients were interviewed to ascertain symptom prevalence, severity and distress using the MSAS and levels of fatigue using the Piper Fatigue Scale (PFS). Sixty-six patients with metastatic cancer and 69 patients with end-stage disease were enrolled in the study. There was a significant difference in the prevalence of selected physical symptoms, but not psychological symptoms, between cancer and noncancer patients. There were no significant differences in symptom distress scores, a computed score of frequency, severity and distress, if the symptom was present. In both groups the principal components factor analysis with varimax rotation yielded one factor comprising psychological symptoms and a second factor comprising three subgroups of physical symptoms. Internal consistency was high for the psychological subscale (Cronbach alpha coefficients of 0.85 for the cancer group and 0.77 for the noncancer group) and for the physical subscale groupings, with coefficients ranging between 0.78 to 0.87. The symptom scores were significantly correlated with perceptions of fatigue. These findings show that both seriously ill cancer and noncancer patients experience symptom distress, and that the MSAS seems to be a reliable measure of symptom distress in noncancer patients, as well as with cancer patients.