In vivo volume growth of two murine tumor cell lines was compared by mathematical modeling to their volume growth as multicellular spheroids. Fourteen deterministic mathematical models were studied. For one cell line, spheroid growth could be described by a model simpler than needed for description of growth in vivo. A model that explicitly included the stimulatory role for cell-cell interactions in regulation of growth was always superior to a model that did not include such a role. The von Bertalanffy model and the logistic model could not fit the data; this result contradicted some previous literature and was found to depend on the applied least squares fitting method. By the use of a particularly designed mathematical method, qualitative differences were discriminated from quantitative differences in growth dynamics of the same cells cultivated in two different three-dimensional systems.