To explore overall survival (OS) and GISTs-specific survival (GSS) among cancer survivors developing a second primary gastrointestinal stromal tumors (GISTs). We conducted a cohort study, where patients with GISTs after another malignancy (AM-GISTs, n = 851) and those with only GISTs (GISTs-1, n = 7660) were identified from the Surveillance, Epidemiology, and End Results registries (1988-2016). Clinicopathologic characteristics and survival were compared between the two groups. The most commonly diagnosed first primary malignancy was prostate cancer (27.7%), followed by breast cancer (16.2%). OS among AM-GISTs was significantly inferior to that of GISTs-1; 10-year OS was 40.3% vs. 50.0%, (p < 0.001). A contrary finding was observed for GSS (10-year GSS 68.9% vs. 61.8%, p = 0.002). In the AM-GISTs group, a total of 338 patients died, of which 26.0% died of their initial cancer and 40.8% died of GISTs. Independent of demographics and clinicopathological characteristics, mortality from GISTs among AM-GISTs patients was decreased compared with their GISTs-1 counterparts (HR, 0.71; 95% CI, 0.59-0.84; p < 0.001), whereas OS was inferior among AM-GISTs (HR, 1.11; 95% CI, 0.99-1.25; p = 0.085). AM-GISTs patients have decreased risk of dying from GISTs compared with GIST-1. Although another malignancy history does not seemingly affect OS for GISTs patients, clinical treatment of such patients should be cautious.