The growing potential of modern molecular analysis tools has led to a sharp increase in the understanding of the molecular dimension of pathological processes and, consequently, to a growing influence of pathological diagnoses on the selection of therapeutic approaches. Molecular analysis tools have also led to the understanding that groups of tumors hitherto considered to belong to a single, homogeneous disease entity should rather be divided into subgroups with specific molecular attributes, growth behavior patterns and, consequently, different prognostic characteristics and therapeutic needs. A major factor contributing to the differentiation of these subgroups is the composition of the tumor microenvironment (ME), a compartment that is involved in the control of critical carcinogenetic processes such as angiogenesis and invasive growth. Consequently, the investigation of the ME promises to be a most auspicious field of research for pathologists and there is hope that the increased understanding of the interaction between neoplastic cells and the ME will lead to improved diagnostic tools and novel therapeutic approaches for the treatment of cancer patients.