columnar/cuboidal epithelial cell differentiation GO:0002065 The process in which a relatively unspecialized cell acquires specialized features of a columnar/cuboidal epithelial cell. A columnar/cuboidal epithelial cell is a cell usually found in a two dimensional sheet with a free surface. Columnar/cuboidal epithelial cells take on the shape of a column or cube. epithelial cell differentiation