Abstract
Background and Objectives: Cancer recurrence represents treatment failure; the development of new primary tumors is suggestive of persistent exposure to etiological risk factors or genetic predisposition due to mutations in multiple cell lines. Case presentation/Design/Methods: The first case is a 65-years-old Caucasian male who presented with esophageal and lung cancer diagnosed synchronously. Smoking was the common risk factor for both cancers, underscoring field cancerization. The diagnosis and management was a challenge and different from either cancer presenting alone. Multidisciplinary approach was used and led to good outcomes. The second case is a 72-years-old Caucasian male presenting a rare dilemma of genetic mutation leading to multiple primary gastrointestinal cancers in a single individual. The gene explaining this group of cancers has not been diagnosed yet and the field needs to be explored further. Conclusion: Multiple primary cancers can be secondary to a common environmental risk factor or genetic mutations.