It has recently been established that the microenvironment plays a major role in many physiological and pathological events. Indeed cell-cell and cell-extracellular matrix contacts are necessary for much cellular function such as differentiation, proliferation, cell death, apoptosis and angiogenesis. For growth, proliferating tumour cells need to be fed by nutrients and oxygen brought by new vessels. In this context, scientists seek a new model that allows for the investigation of both angiogenesis and the influence of the microenvironment on this phenomenon. The purpose of this paper is to review the literature on the relation between tumour and endothelial cells grown as spheroids, a technique that allows us to study in three-dimensions the influence of cell contact on this growth. For the purpose of clarification, this review has recategorised the different studies on spheroids into three classes: (1) spheroids grown in vitro and then reimplanted in animals to follow endothelial cell infiltration;
(2) spheroids grown in vitro and then cultured on endothelial cell monolayers; (3) tumours grown in vitro such as organotypic culture. This review attempts to demonstrate that spheroid cell cultures are useful for studying the relation between tumour and endothelial cells and to analyse physiological phenomena such as wound healing, extravasation and intravasation.