The Gcm1 gene encodes a transcription factor that is essential for both syncytiotrophoblast differentiation and formation of chorionic villi in mice. Its early expression is very unusual in that it defines a subset of trophoblast cells in the chorion, a layer that otherwise contains trophoblast stem cells. While Gcm1 mRNA expression initiates independently within the chorion, the subsequent maintenance of mRNA expression as well as the onset of protein accumulation is dependent on contact with allantoic mesoderm. Previous studies have shown that human GCM1 mRNA and protein are detectable in the placenta, but their patterns have not been compared nor precisely localized. We, therefore, conducted the present study to determine if the human mRNA and protein are subject to the same complexities of regulation as the mouse. In situ hybridization studies showed that the GCM1 mRNA was expressed in villous cytotrophoblast cells, but only a subset and never within cells immediately at the base of columns. Interestingly, the mRNA was detected throughout the cytotrophoblast columns. GCM1 protein expression studies demonstrated that the transcription factor was present mainly within the nuclei of a subset of cytotrophoblast cells, consistent with its role as a transcription factor. Feint cytoplasmic staining of the transcription factor was found in the syncytiotrophoblast but not in aggregated syncytial nuclei. Nuclear immuno-reactivity for the GCM1 protein was detected in occasional nuclei in the distal part of the column. Therefore, GCM1 expression is regulated both at the transcriptional and translational level. Overall, these studies show that the general features of GCM1 mRNA and protein expression in the human placenta are conserved with the mouse. They also highlight the fact that villous cytotrophoblast cells are extremely heterogeneous with respect to GCM1 expression, a factor that should be considered when using isolated cytotrophoblast cells for culture studies.