Pancreatic cancer patients have not benefited from the rising tide of improved overall cancer survival brought about by precision medicine. However, a small subgroup of pancreatic cancer patients have exceptional outcomes. Rare tumor mutations also define small subgroups of pancreatic cancer patients who may respond to the targeted therapies that match to the rare mutations. Prospective clinical trials with a large sample size are unlikely be developed to investigate such small subgroups of patients. This special column is thus established for sharing the knowledge on these small subgroups of patients and for inspiring the development of new concepts and strategies of identifying the biological determinants that define these small subgroups and subsequently tailoring their management.