Although their disease processes and treatments are different, patients with motor neurone disease (MND) and those with late-stage cancer share a common situation--one in which the quality of life, rather than a cure, becomes the focus of care. We report here a comparison of 126 patients with MND and 125 with metastatic cancer on a range of physical and psychosocial measures. Compared to cancer patients, MND patients were younger, had greater social contacts, but were more physically impaired. Cancer patients had more pain and were on more medication (opioids, steroids, and analgesics). Although the Beck depression scores were similar in both groups, MND patients had significantly higher scores for demoralization, hopelessness, and suicidal ideation. Cancer patients, on the other hand, scored significantly higher on anhedonia. We suggest this difference in the quality of depression represents a difference in illness experience of the two groups and has relevance for the ways we treat depression in the medically ill.