Mutations in FLT3 and NPM1 are important prognostic factors in AML, influencing outcome in normal karyotype cases. We here analysed incidences of FLT3/ITD, D 835 and NPM1 mutations in patients with de novo normal karyotype AML using PCR and gene sequencing, along with laboratory parameters and treatment outcomes. There were 128 patients with a median age of 45 years (range, 19-65). FLT3/ITD mutations were detected in 26 (20.3%), FLT3/D835 in 8 (6.2%) and NPM1 in 22 (17.1%). The incidence of FLT3/ITD was higher in those with elevated lactate dehydrogenase (LDH) and peripheral blasts (p=< 0.002, < 0.001) while NPM1 mutations or both NPM1 and FLT3/ITD was more common in elevated total leukocyte counts (TLC), LDH and peripheral blasts (p=<0.0001). Complete response and disease free survival were lower in those with FLT3/ITD mutations (p=0.04, 0.03). The incidence of FLT3 and NPM1 mutations was found to be low in Indian patients with normal karyotype AML.