Barrett’s oesophagus is a condition associated with gastric reflux that increases the chance of developing oesophageal cancer by 30-fold. A key question is how Barrett’s oesophagus arises from normal gastrointestinal tissue. However, because there are several different types of cells within Barrett’s oesophagus, research into the cellular origins of this tissue is difficult. To overcome this challenge, Ludwig Oxford’s Richard Owen, Michael White and David Severson from Xin Lu’s and Benjamin Schuster-Böckler’s labs performed single cell RNA sequencing on patient biopsies from Barrett’s and normal oesophagus. Their results, published in Nature Communications, show that a cell population in Barrett’s oesophagus had most similarity to normal oesophageal submucosal gland cells. This finding has implications for the clinical diagnosis of Barrett’s oesophagus.