The article reviews spherical cancer models, which are three-dimensional (3D) in vitro models used in cancer research. These models, characterized by their well-rounded shape and the presence of cancer cells, have gained popularity in studying cancer stem cell (CSC) properties and tumor behavior. The authors classify four main types of spherical cancer models: multicellular tumor spheroids (MCTS), tumorospheres, tissue-derived tumor spheres (TDTs), and organotypic multicellular spheroids (OMSs). Each model is characterized by different culture methods and biological properties, making them suitable for specific applications such as studying chemoresistance, radioresistance, tumorigenicity, and invasion. The article also discusses the challenges in nomenclature and the importance of selecting the appropriate model based on the research aim and cancer type. The biological characteristics of each model, including their spatial organization, differentiation, and interactions with the extracellular matrix, are detailed, highlighting their relevance to in vivo tumor behavior. Finally, the applications of these models in studying radioresistance, chemosensitivity, migration, and invasion are reviewed, emphasizing their utility in drug testing and personalized treatment strategies.The article reviews spherical cancer models, which are three-dimensional (3D) in vitro models used in cancer research. These models, characterized by their well-rounded shape and the presence of cancer cells, have gained popularity in studying cancer stem cell (CSC) properties and tumor behavior. The authors classify four main types of spherical cancer models: multicellular tumor spheroids (MCTS), tumorospheres, tissue-derived tumor spheres (TDTs), and organotypic multicellular spheroids (OMSs). Each model is characterized by different culture methods and biological properties, making them suitable for specific applications such as studying chemoresistance, radioresistance, tumorigenicity, and invasion. The article also discusses the challenges in nomenclature and the importance of selecting the appropriate model based on the research aim and cancer type. The biological characteristics of each model, including their spatial organization, differentiation, and interactions with the extracellular matrix, are detailed, highlighting their relevance to in vivo tumor behavior. Finally, the applications of these models in studying radioresistance, chemosensitivity, migration, and invasion are reviewed, emphasizing their utility in drug testing and personalized treatment strategies.