SATB2 (special AT-rich sequence binding 2) is a 733-amino acid human DNA-binding protein involved in transcriptional regulation and chromatin remodeling (1,2). SATB2 protein expression in normal human tissue was found in the epithelium of the lower gastrointestinal tract (including appendix, colon, and rectum), as well as specific neurons (in the cerebral cortex and hippocampus), non–germinal center lymphoid cells, and the ductal epithelium of the testis and epididymis (3). In cancer tissues, SATB2 was shown to be almost exclusively expressed in colorectal carcinoma (3). This observation was followed by validation using colorectal cancer tissue from 9 different research cohorts (1558 localized and 252 metastatic colorectal adenocarcinoma). Using SATB2 as a solitary marker, SATB2 showed positive immunostaining in 92.4% (110 of 119) of stage I, 91.4% (402 of 440) of stage II, and 83.7% (431 of 515) of stage III/IV colorectal adenocarcinomas. The expression of SATB2 was analyzed in a prospective study of 840 cases in which CK20 was being used to reach a final diagnosis (4). As a solitary marker, SATB2 had a 93% sensitivity and 77% specificity in diagnosing colorectal carcinoma, but when used as a marker in combination with CK20 positivity and CK7 negativity the sensitivity was 83% and the specificity was 100% in determining colorectal origin (4). SATB2 may be useful in the common differentials of distinguishing adenocarcinomas of colorectal origin from those of gastric and pancreatic origin. SATB2 expression was analyzed in 1941 malignancy cases using tissue microarrays, and shown to be highly expressed in colorectal adenocarcinoma (96.8%; 121 of 125), with low expression in gastric adenocarcinoma (0%; 0 of 20) and pancreatic adenocarcinoma (4.2%; 4 of 95) (5). Additional studies have verified that SATB2 could serve as a clinically useful diagnostic marker for colorectal carcinomas, especially if used in a panel approach (5-8).