Thyroid transcription factor 1 (TTF-1) is an immunohistochemical marker in the identification of lung and thyroid tumors. However, positive labelling for TTF-1 can occur in tumors from other sites, and this can result in misdiagnosis if only a limited panel of antibodies is used. We assessed the frequency of expression of 3 TTF-1 antibody clones, namely, 8G7G3/1, SPT24, and SP141 on a tissue microarray of 104 colorectal cancer (CRC), and whole-tumor sections of 165 CRC with known microsatellite instability (MSI) status. We also analyzed the expression of TTF-1 in a tissue microarray of 112 prostatic adenocarcinomas. The association of TTF-1 expression with clinicopathologic parameters and patient survival was analyzed. Six of 104 (5.7%) primary colorectal carcinomas expressed TTF-1 with SPT24 and SP141 clones, whereas only 2 (2%) of these tumors labeled positive for TTF-1 with clone 8G7G3/1. A significant association of TTF-1 expression with younger age at diagnosis (P=0.001) was found, but not with stage, or survival. The SP141 clone also labelled 24/165 (14.5%) of 165 CRC with known MSI status. There was an association with younger age (P<0.001), but not with MSI status or survival. TTF-1 expression was found in 39/112 (34%) prostate adenocarcinomas with 6/112 (5.3%) labelling with clone 8G7G3/1, 26/112 (23%) with clone SP141, and 31/112 (28%) with clone SPT24. TTF-1 expression appeared to be associated with extracapsular extension (P=0.022) and with higher stage (P=0.039). Here too TTF-1 expression was not associated with survival. The mRNA expression of TTF-1 in these tumors was confirmed by RTPCR, indicating that this is not false-positive labelling. Depending on the clone used, TTF-1 expression can vary with the SP141 and SPT24 clones exhibiting higher incidence of labelling. Pathologists should be aware of the differences in performance profiles of the different TTF-1 clones in diagnostic practice.