Introduction: Three-dimensional cell spheroids bred under in vivo conditions exhibit a complex architectural structure, dynamic cell interactions as well as a high potential of mimicking complex three-dimensional tissue organization in vivo. Cellular spheroids are powerful means of narrowing the gap between in vitro and in vivo models. It is possible to grow cellular spheroids with different breeding techniques which, depending on the cell line and research needs, give a different spheroid formation. Research objectives: The aim was to study possible morphological differences between cellular spheroids cultivated by different breeding methods. Materials and methods: . We planted the HeLa, CaCo-2, and NCI-H358 cell lines in 2D and 3D formats using three different methods - the hanging drop method, the forced floating method and the gel cell cultivation. We monitored and imaged spheroid formation within ten days using a light microscope. We used flow cytometry to analyse the cell cycle of grown cells. Results: HeLa cell line showed the fastest growth in all three methods, while the slowest was the NCI-H358. The most proper spheroids were formed in all cell lines using the hanging drop method. The cell cycle analysis showed that the largest proportion of cells lies within the G1 phase. Conclusion: By applying different methods of breeding cell spheroids there is no major difference in the morphology of the individual cell lines; all methods yielded round spheroidal structures. However, the most proper spheroids were obtained by the hanging drop method. The distribution of cells within the cell cycle during the incubation does not change significantly; the largest proportion of cells is in the G1 phase.