Eukaryotic translation initiation factor 4E (eIF4E) is a rate-limiting factor for cap-dependent protein synthesis and is regulated by PI3 kinase/mTOR and mitogen-activated protein kinase (MAPK)/Mnk signaling pathways. Recent studies have shown that Mnk-mediated eIF4E phosphorylation is absolutely required for eIF4E's oncogenic function. Overexpression of eIF4E has been reported in many types of cancers; however, the expression of phosphorylated eIF4E (p-eIF4E) in human cancer tissues, particularly solid tumor tissues, has not been reported. The current study focused on evaluating p-eIF4E expression patterns in the tumor tissues obtained from patients with a variety of malignancies. Using three different tissue microarrays consisting of a total of 380 cases of human cancers and 146 cases of adjacent normal tissues, we detected p-eIF4E positive staining in 63.4% (241/380) of cancers, but only in 30.1% (44/146) of adjacent normal tissues. Thus, p-eIF4E expression is significantly higher in cancers than in adjacent normal tissues (p < 0.001). In general, there was no major difference in p-eIF4E staining between cancers with and without lymph node metastasis. In certain types of maligancies such as lung, gastric and colorectal cancers, p-eIF4E staining was significantly higher in the early stage (T1) than in the late stage (T3) disease (p < 0.05). Collectively, these findings suggest that p-eIF4E may play a critical role in cancer development, particularly early stages of tumorigenesis and support p-eIF4E as a good cancer therapeutic target.