Acute myeloid leukemia (AML) is a highly malignant disease of myeloid cell line. AML is the most frequent adult leukemia with inadequate treatment possibility. The protein phosphatases are critical regulators of cell signaling, and deregulation of protein phosphatases always contribute to cell transformation. Although many studies established a relationship between protein phosphatases and leukemia, little is known about the role of this group of proteins in AML. To address this issue, we initially identified the complete catalog of human protein phosphatase genes and used this catalog to study deregulation of protein phosphatases in AML. Using mRNA expression data of AML patients, we show that 11 protein phosphatases are deregulated in AML within 174 protein phosphatases. The GO enrichment study suggests that these genes are involved in multiple biological processes other than protein de-phosphorylation. Expression of DUSP10, PTPRC, and PTPRE was significantly higher than average expression in AML, and a linear combination of DUSP10, MTMR11, PTPN4, and PTPRE expressions provides important information about disease subtypes. Our results provide an overview of protein phosphatase deregulation in AML.