More than 50% patients with GISTs have metastasis at the time of presentation. Most common sites of metastasis are liver and peritoneum followed by lungs and bones. Presence of metastasis, heterogeneous enhancement, tumor size more than 5 cm, necrotic changes, ulceration, cystic changes and hemorrhage are signs of malignancy in GISTs.

GIST is resistant to a standard chemo- and radiotherapy. The only curative treatment is radical surgical excision. The effects of treatment of inoperative or metastatic GISTs were, until recently, very poor (median survival after recurrence was 9–20 months). However, in recent years there have appeared radical changes in the therapy of advanced tumors due to the discovery and implementation of treatment with tyrosine-kinase inhibitors. GIST has been the first solid tumor treated with an advanced molecular targeting therapy since 2001, when Imatinib was introduced.