Abstract: Chronic Myeloid Leukemia (CML) is a chronic disease that about 50% of patients are more than 60 years old and about 50% of patients are asymptomatic. In this study, It is reported that, a case of CML after colon cancer chemotherapy in a 52 year old male from Iran who diagnosed locally advanced poorly differentiation colon adenocarcinoma with extension to prostate for him that had undergone to chemotherapy induction, then chemoradiation with surgery for mid-rectal cancer in the follow-up with picture of local recurrence and rectovesical-fistula. His first regimen in induction chemotherapy phase been oxaliplatin plus capecitabine and follow with chemoradiation for one month. The KRAS was mutation for the patient. He treated with combination of capecitabine with bevacizumab. After new progression he treated with Xeloda+irinotecan regimen. In routine follow-up in complete blood count analysis, It was found that shift to left with immature granulocytopoietic forms. Analysis by RT-PCR peripheral blood showed that Philadelphia chromosome was positive, so CML was diagnosed for him and was add imatinib to his treatment policy. Combination of oxaliplatin and irinotecan can be carcinogenic even they can probably create secondary hematological malignancy like CML and also irradiation can be other risk factor in patients with colorectal cancer following chemotherapy.