The primary origin of some ovarian mucinous tumors may be challenging to determine, because some metastases of extraovarian origin may exhibit gross, microscopic, and immunohistochemical features that are shared by some primary ovarian mucinous tumors. Metastases of primary colorectal, appendiceal, gastric, pancreatic, and endocervical adenocarcinomas may simulate primary ovarian mucinous cystadenoma, mucinous borderline tumor, or mucinous adenocarcinoma. Recently, immunohistochemical expression of SATB2, a transcriptional regulator involved in osteoblastic and neuronal differentiation, has been shown to be a highly sensitive marker of normal colorectal epithelium and of colorectal adenocarcinoma. SATB2 expression has not been reported in normal epithelium of the female reproductive tract. Therefore, we hypothesized that SATB2 may be of value in distinguishing ovarian metastases of colorectal adenocarcinoma from primary ovarian mucinous tumors and from primary ovarian endometrioid tumors. Among primary ovarian tumors, SATB2 staining was observed in 0/22 mucinous cystadenomas that lacked a component of mature teratoma, 4/12 mucinous cystadenomas with mature teratoma, 1/60 mucinous borderline tumors, 0/17 mucinous adenocarcinomas, 0/3 endometrioid borderline tumors, and 0/72 endometrioid adenocarcinomas. Among ovarian metastases, SATB2 staining was observed in 24/32 (75%) colorectal adenocarcinomas; 8/10 (80%) low-grade appendiceal mucinous neoplasms; and 4/4 (100%) high-grade appendiceal adenocarcinomas. No SATB2 staining was observed in any ovarian metastasis of pancreatic, gastric, gallbladder, or endocervical origin. Evaluation of primary extraovarian tumors showed the highest incidences of SATB2 staining among primary colorectal adenocarcinomas (71%), primary appendiceal low-grade mucinous neoplasms (100%), and primary appendiceal high-grade adenocarcinomas (100%). Similar to their metastatic counterparts, none of the primary pancreatic or gastric adenocarcinomas showed any SATB2 staining. In a subset of tumors for which CK7, CK20, and CDX2 were available, SATB2 was never positive in any tumor of any origin that was CK7CK20CDX2. Among tumors that coexpressed all 3 markers (CK7CK20CDX2), 6/7 SATB2 tumors were of colorectal or appendiceal origin, and 1/7 was a primary ovarian borderline tumor. We conclude that ovarian tumors with mucinous or endometrioid features that express SATB2 are unlikely to be of primary ovarian origin unless there is a component of mature teratoma in the ovary; instead, attention should be directed to a colorectal or appendiceal origin. SATB2 may be of particular value in ovarian mucinous tumors that are positive for all 3 markers (CK7CK20CDX2), as SATB2 staining strongly implicates a colorectal or appendiceal origin.