The quality of life (QoL) evaluation can better contextualize the psychosocial problems experienced by patients over the disease trajectory, as well as, monitor the quality of cancer care and the efficacy of psychosocial intervention/treatment. Moreover, elevated level of distress have been linked with reduced health-related QoL. A longitudinal study was carried out to investigate the relationship between high level of distress (DT ≥ 4) and QoL, throughout the chemotherapy. For this assessment was considered three points in the treatment protocol, with an average interval of two and a half months between them (first day - T1; middle - T2; last day - T3). A sample of 161 patients, completed the Distress Thermometer and the Functional Assessment of Cancer Therapy - General. Of those, 29.8% were male and 70.2% female, with a mean age of 56 years (SD = 14.9; range 19-84 years). The main forms of cancer were gastrointestinal (33.4%), breast (29.8%) and hematological (21.7%). About 36.4% had early stage (I and II) disease and 63.6% late stage (III and IV). At T1 distress level was significant related to QoL score (r = -.73, p < .001) and QoL to disease stage (r = -.16, p < .05). At T2 and T3 distress was related to QoL (r = -.65, p < .001; r = -.59, p < .001). Accordingly with this preliminary data distress was related to QoL over all treatment phases: fear of the unknown (T1), adaptation to side effects and the cancer reality (T2) and apprehension with the end of treatment (T3); and the disease stage just with QoL at T1. This results suggest the importance of distress and QoL screening routine, since this allows an in-depth look at the patient’s psychosocial health care needs, improving not only the psychosocial service as the quality of cancer care.