Chronic myeloid leukemia is one of the myeloproliferative disorders characterized by t(9;22) (q34;q11) known as Philadelphia chromosome. This leads to the formation of a fusion gene Bcr-Abl tyrosine kinase having properties necessary for malignant transformation. Imatinib is a leading tyrosine kinase inhibitor that showed marked cytogenetic responses, but sometimes out casted by presence of resistance. Resistance has been traced mainly to occurrence of mutations within Bcr-Abl domain making it insensitive to Imatinib. Our aim is to determine the presence of Bcr-Abl kinase domain mutations among chronic myeloid leukemia patients before and during therapy with Imatinib. 24 patients at different phases of the disease were recruited and mutation analysis was done using ASO-PCR for 3 mutations: T315I, M351T, and E255K. One patient with accelerated phase CML demonstrated presence of M351T mutation and switched to second generation tyrosine kinase inhibitor Nilotinib. Further large scale studies are recommended to detect presence of Bcr-Abl mutations and assess their frequency among Egyptian chronic myeloid leukemia.