Cells of the highly diverged Schizosaccharomyces (S.) pombe and S. japonicus fission yeasts exist in one of two sex/mating types, called P (for plus) or M (for minus), specified by which allele, M or P, resides at mat1. The fission yeasts have evolved an elegant mechanism for switching P or M information at mat1 by a programmed DNA recombination event with a copy of one of the two silent mating-type genes residing nearby in the genome. The switching process is highly cell-cycle and generation dependent such that only one of four grandchildren of a cell switches mating type. Extensive studies of fission yeast established the natural DNA strand chirality at the mat1 locus as the primary basis of asymmetric cell division. The asymmetry results from a unique site- and strand-specific epigenetic "imprint" at mat1 installed in one of the two chromatids during DNA replication. The imprint is inherited by one daughter cell, maintained for one cell cycle, and is then used for initiating recombination during mat1 replication in the following cell cycle. This mechanism of cell-type switching is considered to be unique to these two organisms, but determining the operation of such a mechanism in other organisms has not been possible for technical reasons. This review summarizes recent exciting developments in the understanding of mating-type switching in fission yeasts and extends these observations to suggest how such a DNA strand-based epigenetic mechanism of cellular differentiation could also operate in diploid organisms.