Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are reported in acute myeloid leukemia (AML). We studied the frequency and the clinicopathologic features of IDH1 and IDH2 mutations in AML. Mutations in IDH1 (IDH1^R132) and IDH2 (IDH2^R172) were assessed by Sanger sequencing in 199 AML cases. Point mutations in IDH1^R132 were detected in 12 (6.0%) of 199 cases and in IDH2^R172 in 4 (2.0%) of 196 cases. Of the 16 mutated cases, 15 (94%) were cytogenetically normal, for an overall frequency in this group of 11.8%. IDH1^R132 and IDH2^R172 mutations were mutually exclusive. Concurrent mutations in NPM1, FLT3, CEBPA, and NRAS were detected only in AML with the IDH1^R132 mutation. The clinical and laboratory variables of patients with AML with IDH mutations showed no significant differences compared with patients with wild-type IDH. We conclude that IDH1^R132 and IDH2^R172 mutations occur most often in cytogenetically normal AML cases with an overall frequency of approximately 11.8%.