The present study evaluated the effects of physical exercise on heart rate variability (HRV) in cancer patients. 3 matched groups of each 15 tumour patients (60.4+/-8.9 years, 27 male, 18 female) were recruited: Physical exercise group 1 (acute treatment), Physical exercise group 2 (post treatment) and non-intervention group (acute treatment, no exercise). Exercise group patients received counselling for exercise and participated in a Nordic-Walking program. Short-term HRV-recordings, assessments of fatigue and quality of life (QoL) were performed prior to and 16 weeks after the exercise program initiation. MANCOVA revealed group x time differences in total power frequency domain of HRV and QoL (p<0.05). TP follow-up scores [logms(2)] differed significantly between non-intervention and intervention post treatment (2.0+/-0.5 vs. 2.6+/-0.5), but not between non-intervention and intervention during acute treatment. QoL follow-up scores differed significantly between non-intervention and intervention during acute treatment (47+/-15 vs. 64+/-18) and post treatment (47+/-15 vs. 69+/-19). Exercise enhances cardiac autonomic regulation of tumour patients during and after acute treatment. Because of the association of higher HRV-parameters and prolonged survival in cancer patients, improvement in autonomic control may be an important goal of exercise.