Background: Alterations of PTEN, regulator of the PTEN/PI3K-AKT pathway, are common in several types of cancer. This study aimed to do comprehensive analysis of PTEN in colorectal cancer patients. Methods: Totally, 198 colorectal cancer patients who received surgery at Taipei Veterans General Hospital from 2006 to 2008 were enrolled. Mutations, loss of protein expression, promoter hypermethylation, and DNA copy number of PTEN were analyzed by sequencing, immunohistochemistry, methylation-specific polymerase chain reaction PCR, and quantitative (QPCR), respectively, and correlated with clinicopathological features and patients' outcome. Results: Genomic mutations, loss of protein expression, promoter hypermethylation, and decreased DNA copy number of PTEN were found in 4 (2.02 %), 68 (34.3 %), 54 (27.3 %), and 36 (18.2 %) tumors, respectively. Of these 68 tumors with loss expression of PTEN, 34 (50 %) tumors had promoter methylation and 18 (26.5 %) had decreased DNA copy number. All four tumors with PTEN mutations demonstrated loss of PTEN expression. In the stage I disease, frequency of loss of PTEN expression was 20 % and significantly increased to 56.9 % in stage IV disease. Either loss expression of PTEN, PTEN hypermethylation or decreased PTEN copy number was not associated with colorectal cancer (CRC) patients' outcome. Conclusions: PTEN alterations were found in up to one-third of colorectal cancers but did not impact CRC patients' prognosis.