The human OCT4 gene can generate at least three transcripts (OCT4A, OCT4B, and OCT4B1) and four protein isoforms (OCT4A OCT4B-190, OCT4B-265 and OCT4B-164) by alternative splicing and alternative translation initiation. OCT4A is a transcription factor responsible for the pluripotency properties of embryonic stem (ES) cells. While OCT4B cannot sustain ES cell self-renewal, it may respond to cell stresses. Yet the function of OCT4B1 is still unclear. Lack of distinction of OCT4 isoforms could lead to confusions and controversies on OCT4 in various tissues and cells. One important issue we emphasize in this review article is that alternatively spliced transcripts and alternative translation products of OCT4 exhibit diverse expression patterns and functions. Furthermore, simple approaches and methods to detect and distinguish OCT4 isoforms are discussed. This article underscores the importance of identifying and discriminating the expression and functions of OCT4 isoforms in stem cell research.