The aim of the present study was to monitor the health-related quality of life (HRQOL) of patients with head and neck cancer or haematological malignancies during a period from before to after medical treatment, and to investigate the relationships between patient experiences of oral symptoms and HRQOL. The sample consisted of 41 consecutive patients. At the start, during and end of radiotherapy or the second/third cycle of chemotherapy, patients rated their experiences of oral symptoms on a 100-mm visual analogue scale and completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30 and the EORTC QLQ H&N35 (head and neck patients). At the end of treatment, an interview was done regarding the perceived influence of oral status on HRQOL. Among patients receiving radiotherapy, HRQOL tended to decrease over time, and oral symptoms increased. Patients who reported that their oral symptoms had influenced their everyday life (56%) reported more severe oral symptoms and lower HRQOL scores at the end of treatment when the oral symptoms were most intense. The findings from correlational analyses support the patients' reports from the interviews. For patients receiving chemotherapy for haematological malignancies, the quality of life did not change during the chemotherapy cycle. They reported very few oral symptoms, and very few reported that oral symptoms had any influence on their HRQOL. However, the correlational data indicate a relation between oral symptoms and HRQOL. Patients who reported more severe oral symptoms also reported lower HRQOL scores. The results demonstrate that oral status is related to HRQOL in these patient groups.