The classical tissue model of August Krogh remains the cornerstone in the modeling of tissue PO2. However, heterogeneities of O2 determinants can profoundly affect the calculated oxygen fields. One of them is the heterogeneity in capillary spacing. At the present time there are two methods available for the estimation of capillary spacing: the method of capillary domains and the closest-individual method. The former estimates the distribution of the surface areas surrounding each capillary while the latter derives the distribution of distances of tissue points to the nearest capillary. Both can be transformed into the distribution of the radii of tissue cylinders according to the model of Krogh. Their distribution is approximately lognormal and is characterized by the mean (or median) value and the logarithmic standard deviation (log SD), which serves as the heterogeneity index. When applied to the same photomicrographs, both methods give similar values of the mean but the domain method yields a smaller log SD than does the closest-individual method. Subsequently, the calculated tissue PO2 histograms are also more uniform with the domain method. This difference is caused by the asymmetry of the domains. The shape of the domains is not circular and the capillary is not situated in the center as suggested by the model of Krogh. The method of capillary domains, however, is more direct and less time-consuming and thus more suitable for routine work. Nevertheless, the goal of future research is to develop a method that would characterize not only the distribution of the surface area of the domains but also their asymmetry.