There is still no therapy method in the colorectal cancers that is good enough for such a complex disease. Combined surgery, chemotherapy, and radiotherapy improved survival, but the side effects and the poor performance status of the patients seriously affect the use of these methods. We used a therapeutical approach of surgery and chemotherapy combined with biotherapy by Viscum album extract Isorel, aiming to improve the patients' resistance to the disease and to render the treatment's side effects more tolerable. Isorel is aqueous extract well known for its anticancer effects obtained by various in vitro and in vivo experimental models and which was validated by an in vitro bioassay on murine melanoma B16F10 and human cervical carcinoma HeLa cells. Isorel strongly reduced human colon cancer HT 29 cell line growth in vitro in the MTT bioassay. Hence, it was further used in a prospective, randomized, and controlled study which compared the postoperative results for patients with colorectal cancer stages Dukes C (40 patients) and D (24 patients) who, beside surgery, received either only chemotherapy (5-FU), 6 cycles (either the Mayo or the De Gramont protocol) or chemotherapy combined with Isorel biotherapy. These 64 patients were randomly allocated into three groups "only chemotherapy" for 21 cases, chemo + biotherapy for 29 cases and 14 patients underwent only surgery as the control group. We noted no toxic deaths due to either chemo or biotherapy. The patients operated on and treated with chemo and biotherapy had median survival significantly better and a cumulative proportion survival (Kaplan-Maier) superior to those of the patients receiving only postoperative chemotherapy. Thus, colorectal cancer patients seem to benefit in terms of survival from combined postoperative chemotherapy and Isorel biotherapy, either adjuvant or palliative.