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This article summarizes important highlights regarding gastrointestinal cancer at the 2019 ESMO annual meeting. The choice of the abstracts was based on a personal view with a focus on different tumor entities of the gastrointestinal tract. Precision-medicine-guided therapy for cancer entities was one of the main topics at this year’s ESMO. Furthermore, circulating tumor DNA (ctDNA) by performing liquid biopsy was again another hot topic, especially in guiding adjuvant chemotherapy in stage III colorectal cancer (CRC) patients. Finally, hope was stirred up again for immunotherapy in the indication of first-line treatment in nonresectable hepatocellular cancer (HCC). In summary, the astonishing progress in new drugs that has been made in recent years is still ongoing and will lead to better treatment for cancer patients.