All tumour cells arise and develop through harsh microenvironmental selection. They adapt or inherit variations to increase each clone for competition, survival and proliferation. Their relative abilities to survive, proliferate and propagate genes are supported by crosstalk with surrounding stromal cells. As a result, tumour cells gain the hallmarks of cancer and emerge as more malignant for metastasis and resistant to therapies. This seminar will review various interactions of tumour with stromal cells in the tumour microenvironment.