Background: Esophageal cancer causes an estimated 400,000 deaths per year and ranks as the sixth leading cause of cancer death worldwide, just after breast cancer. Esophageal squamous cell carcinoma (ESCC) accounts for 89% of all esophageal cancer cases worldwide and many of the cases originate in two high risk regions, one in Asia and the other in Africa. Smoking tobacco and heavy alcohol consumption do not explain the incidence rates in the high-risk regions. It is therefore important to consider a wide range of etiologic factors to explain the high rates of cancer in these populations. Malawi has the highest incidence rates of ESCC in Africa. Our previous studies in Kenya and preliminary studies in Malawi point to a number of potential ESCC risk factors.