Translatability of findings is one of the greatest challenges in preclinical oncology. A variety of animal models have been generated in cancer research, however physiological models that faithfully mimic human cancers are lacking. In addition, with the development of increasingly complex immunotherapies more relevant and accurate preclinical models are required. Genetically engineered mouse models (GEMMs) are widely used to investigate disease-specific mutations in organ-dependent contexts, but they develop de novo tumours and exhibit long tumour latencies, which make them not suitable for large-scale in vivo pharmacological studies. An alternative approach is the use of xenografts and allografts. While the xenograft model is used for transplantation of patient-derived tumours or human cell lines into immunodeficient mice, the allograft model enables the implantation of syngeneic cell lines, which are derived from primary GEMM tumours and metastases, into the complex microenvironment of immunocompetent animals. For the generation of cancer xenografts and allografts, heterotopic (i.e., subcutaneous) and orthotopic (organ of native tumour location) implantation methods can be distinguished. In contrast to heterotypic transplantation, orthotopic models enable the investigation of tumour growth, invasion, metastasis and chemosensitivity in the organ (or tissue) that corresponds to the histotype and microenvironment of the tumour material to be implanted. This disease and clinically relevant environment are characterized by the presence of specific growth factors, gender-specific hormones, matrix content, vascularisation, immune responses and microbial signals. The aim of this Methods Collection is to provide an overview of established orthotopic allograft and xenograft models in different organs of various cancer types.