Distress and to some extent health-related quality of life (HRQoL) in head and neck squamous cell carcinoma (HNSCC) patients was found to be stable during follow-up. About one-third of the distress and HRQoL variances were accounted for in the present investigation with one-third from T stage, one-third directly from neuroticism and one-third from neuroticism via choice of coping response. In addition, choice of coping response predicted directly 5% of the HRQoL variance.