Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract, with an incidence of 1.1 cases/100,000 inhabitants/year. A group of experts from the Spanish Society of Pathology and the Spanish Society of Oncology met to discuss a brief update on GISTs and agree on aspects relating to the pathological and molecular diagnosis of these tumors. GISTs are generally solitary, well-circumscribed lesions of variable size (<10 mm-35 cm) that may present with intra- or extra-luminal parietal growth or a mixed-type (hourglass) growth pattern. Histologically, they are unencapsulated neoplasms displaying expansive growth and spindle-shaped (70%), epithelioid (20%), or mixed cellularity (10%). Mitotic activity is generally moderate or low and should be evaluated only in areas with high cellularity or higher mitotic frequency. The great majority of GISTs harbour mutually exclusive activating mutations in genes coding for the type III receptor tyrosine kinases KIT and PDGFRA; less commonly, GISTs have also been reported to display mutations elsewhere, including BRAF and NF1 and SDH-complex genes. The method most widely used to detect KIT and PDGFRA mutations is amplification of the exons involved by polymerase chain reaction followed by direct sequencing (Sanger method) of these amplification products. Molecular analyses should always specify the type of analysis performed, the region or mutations evaluated, and the sensitivity of the detection method employed.