We describe a distinctive tissue artifact that results from the use of biopsy bags for processing small impressionable pieces of tissue. In its fully developed form, the artifact produces a tic-tac-toe pattern, while in less pronounced cases it may produce elongated oval spaces in the tissue or a serrated contour at the periphery of the tissue. The artifact was observed in 60% of endometrial specimens, 55% of endocervical curettings, and sporadically in other small specimens. In the endometrial and endocervical specimens, the artifact was focal and did not interfere with the diagnosis. In occasional small lung and prostate specimens, there was focally significant distortion that potentially could compromise the diagnosis.