Background: Colloid cysts, although benign, may occasionally cause obstructive hydrocephalus and sudden death. Reliable prognostic factors for symptomatic progression have been sought, with heterogenous results. Methods: We conducted a retrospective review of all cases of colloid cysts of the third ventricle managed at our center between 2009 and 2019. Clinical and neuroimaging characteristics were analyzed using logistic regression in relation to symptomatic status and hydrocephalus. The cutoff values for outcome prediction were calculated using the receiver operating characteristic curve analysis. Results: There were 82 patients with colloid cysts, of whom 60 were asymptomatic and 22 symptomatic. None of the asymptomatic patients experienced acute neurologic decline or hydrocephalus during follow-up, whereas half (n = 11) of the symptomatic patients presented with hydrocephalus, 8 of whom had acute hydrocephalus. We found 3 putative candidate risk factors for symptomatic colloid cysts: T1-weighted magnetic resonance imaging hyperintense/mixed signal appearance (P = 0.004), location in risk zone I (P = 0.007), and a volume >236.49 mm 3 (P = 0.007). Cyst diameter and volume/foramen of Monro diameter ratios had a decreasing trend over time among asymptomatic patients, providing new insights into the natural history of the disease. Conclusions: Only a few asymptomatic colloid cysts showed progression requiring surgery, with no acute deterioration or fatal events, whereas the rest remained stable over time, thus supporting a more conservative approach for this group of patients. Higher risk for developing symptomatic colloid cyst was defined by a risk score that included T1-weighted magnetic resonance imaging appearance, risk zone, and colloid cyst volume, aiding the detection of patients at risk of clinical deterioration.