Some male calico or tortoiseshell cats may be chimeras, which result from the fusion in early development of two embryos with different color genotypes. As in humans, these cats are almost always sterile because of the imbalance in sex chromosomes. These animals typically have an extra X chromosome (XXY), a condition known in humans as Klinefelter syndrome, and undergo an inactivation process like that in females. Very rarely (approximately 1 in 3,000 ) a male tortoiseshell or calico is born. Male cats, like other mammalian males, have only a single X chromosome (XY) that does not undergo X-inactivation: coat color is determined by which allele is present on the X, and they will be either entirely black or orange. Each patch represents a clone of cells derived from one original cell in the early embryo. Observation of tri-color cats will show that, with a little white color, the orange and black patches become more defined, and with still more white, the patches become completely distinct. In intermediate cases, melanocyte migration is slowed, so that the pigment cells arrive late in development and have less time to intermingle. In the extreme case, no melanocytes make it to the skin and the cat is entirely white (but not an albino). The amount of white is artificially divided into mitted, bicolor, harlequin, and van, going from almost no white to almost completely white. There are a number of alleles of this gene that produce greater or lesser delays. This spotting gene produces white, unpigmented patches by delaying the migration of the melanocytes to the skin surface. A famous calico, Tama In tri-colored calico cats, a second gene interacts developmentally with the coat color gene. In bi-colored tortoiseshell cats, the melanocytes arrive relatively early, and the two cell types become intermingled, producing the characteristic brindled appearance consisting of an intimate mixture of orange and black cells, with occasional small diffuse spots of orange and black. Pigment genes are expressed in melanocytes that migrate to the skin surface later in development.

Cells in which the Black ( X B) allele is inactivated express the Orange ( X O) allele. The inactivated X becomes a Barr body Cells in which the chromosome carrying the Orange ( X O) allele is inactivated express the alternative Black ( X B) allele. The cells of female cats, which like other mammalian females have two X Chromosome (XX), undergo the phenomenon of X-inactivation, in which one or the other of the X-chromosomes is turned off at random in each cell in very early development. The primary gene for coat color (C) is located on the X Chromosome and has two dominant alleles, Orange ( X O) and Black ( X B), that produce orange phaeomelanin and black eumelanin pigments, respectively. Tortoiseshell and calico coats result from an interaction between genetic and developmental factors. Tortoiseshell also can be expressed in the point pattern.

Occasionally Tabby Cat patterns of eumelanin and pheomelanistic colours are also seen (these are often then called 'torbie', 'torbie' or 'caliby'). The markings on tortoiseshell cats are usually asymmetrical. Dilution genes may modify the coloring, lightening the fur to a mix of cream and blue, lilac or fawn. Typically, the more white a cat has on their fur, the more solid the patches of color. The size of the patches can vary from a fine speckled pattern to large areas of color. Tortoiseshell cats have coats with patches of red, brown or black, chocolate, cream, or cinnamon.

Tortoiseshell calico cat mix