Background. Sampling of submucosal lesions in the gastrointestinal tract through a flexible endoscope is a well-recognized clinical problem. One technique often used is endoscopic ultrasound-guided fine-needle aspiration, but it does not provide solid tissue biopsies with preserved architecture for histopathological evaluation. To obtain solid tissue biopsies from submucosal lesions, we have constructed a new endoscopic biopsy tool and compared it in a crossover study with the standard double cupped forceps. Methods. Ten patients with endoscopically verified submucosal lesions were sampled. The endoscopist selected the position for the biopsies and used the instrument selected by randomization. After a biopsy was harvested, the endoscopist chose the next site for a biopsy and again used the instrument picked by randomization. A total of 6 biopsies, 3 with the forceps and 3 with the drill instrument, were collected in every patient. Results. The drill instrument resulted in larger total size biopsies (mm2; Mann-Whitney U test, P =.048) and larger submucosal part (%) of the biopsies (Mann-Whitney U test, P =.003) than the forceps. Two patients were observed because of chest pain and suspicion of bleeding in 24 hours. No therapeutic measures were necessary to be taken. Conclusion. The new drill instrument for flexible endoscopy can safely deliver submucosal tissue samples from submucosal lesions in the upper gastrointestinal tract.