Despite the devastating motor impairment, a significant number of patients with amyotrophic lateral sclerosis (ALS) maintain a good psychosocial adjustment. Here we investigated whether this is specific for ALS or a more general characteristic of terminal disease. Psychosocial adjustment was investigated in 30 ALS patients, 29 cancer patients in palliative treatment and 29 age-, gender- and level of education-matched healthy controls. Subjective quality of life (sQoL), degree of depressive symptoms and coping were evaluated as measures of psychosocial adjustment. Personality factors were described. ALS and cancer patients showed a good psychosocial adjustment. Subjective QoL and depression did not differ significantly. Both patient groups presented a good sQoL. The level of mild depressive symptoms in both patient groups was similar and none showed clinically relevant depression. ALS patients expressed fewer active coping strategies than cancer patients which were explained by gender differences. Both patient groups showed comparable psychosocial adjustment to their disease. Overall, in terminally ill patients the psychological response to the prognosis is not associated with neurobiological changes (e.g., associated with subclinical deficits in ALS) or with physical decline.