Cancer is one of the most frequent causes of death in Germany. The reasons of various cancer diseases still remain uncertain. There is a long-standing discussion about associations between personality, depression, stress, and stressful life events, respectively, and the development of malignant neoplasms. Evidence for a role of psychosocial factors in development of cancer is not unequivocal despite many years of research on the subject. Current prospective investigations do not support the conventional wisdom of a direct influence for personality in the development of cancer. Much of the research has been impaired by methodological flaws such as inadequate sample size, failure to adjust for potential confounders, lengths of follow-up, use of a variation of different measurements of cancer, and psychosocial variables. Furthermore, specific personality traits and various life events are associated with certain health-related behavior and lifestyle factors, e.g., smoking or an unhealthy nutrition. These unhealthy habits can increase cancer risk. Psychological parameters may alter immune and endocrine function and it has long been hypothesized that, through this pathway, psychosocial factors may affect cancer incidence. In conclusion, study results to substantiate the role of psychosocial factors in the development of various cancers are inconclusive. Contradictory results may be explained by methodological shortcomings. Further studies are required to pursue this question further.