Although the notion that tumors are heterogeneous is well rooted in diagnostic pathology, the extent of this heterogeneity at the molecular level and its impact on (targeted) treatment choice will certainly influence the practice of pathology. Even though the consequences of tumor heterogeneity for cancer care are as yet incompletely understood, pathologists can contribute to solving major scientific and clinical problems related to tumor heterogeneity by rethinking guidelines for tumor sampling, to have a more comprehensive covering of intratumor heterogeneity in the available tumor tissue samples. They should develop guidelines and/or technology to adequately document sample characteristics such as percentage of tumor cells in a sample. They need to contribute to training of bioinformaticians in the field of cancer pathobiology and integrate such well-trained bioinformaticians in the workflow leading to a final pathology report. They also need to redefine postgraduate training programs in diagnostic pathology to address the need for in-depth training in molecular cancer pathobiology. Pathologists might contribute more to making the public at large aware of the importance of data sharing. Finally, pathologists should support the creation of consortia in which clinical and molecular data are shared with the translational research community.