Abstract: CYP3A4 is the monooxygenase enzyme that interacts in the metabolism of great majority of drugs, especially in chemotherapeutic regimens which include combination of drugs. It is believed that by controlling a patient`s CYP3A4 expression level one could adjust the individual dose adjustments in therapies and may also be able to identify the subpopulation at increased risk for several common cancers. This belief prompted us to undertake this investigation. In this study we present the results of CYP3A4 mutations in a large number of breast cancer patients undergoing chemotherapy after surgery. Blood samples collected from post chemo patients (n = 30) administered with 5-Fluorouracil, Doxorubicin and Cyclophosphamide (FAC) drugs were analyzed for CYP3A4 polymorphisms. These samples were from among the first, third and sixth cycle regimen of chemotherapy. DNA extracted from all the blood samples was used for PCR amplification of CYP3A4, followed by sequencing in automated ABI 3770 sequencer. Biochemical tests performed on these blood samples included Liver Function Tests (LFT`s). These investigations were also carried out on equal number (n = 30) of age matched individuals. We found 2 novel Single Nucleotide Polymorphisms (SNP`s) in exon-10 (L338F and I334T) of CYP3A4 and also found that these patients showed elevated Liver Function Tests (LFT) and ADR`s such as alopecia, nausea, vomiting, neuro toxicity, GI toxicity, bone marrow suppression and leucopenia. It was also seen that asingle base change in the 5` flanking region of the CYP3A4 gene wasassociated with severe ADR`s in breast cancer chemotherapy patients. It is concluded that mutations in CYP3A4 gene influences drug metabolism leading to adverse drug reactions in post chemo breast cancer patients.