Purpose: To report the presenting signs of retinoblastoma in a large cohort of patients who underwent orthoptic assessment at presentation. Methods: A retrospective medical chart review was conducted on 131 patients with retinoblastoma who presented consecutively to a single institution during a 6-year period. The main outcome measure was the presenting sign(s) of the disease. Results: Of 131 patients with retinoblastoma, 88 presented with unilateral disease and 43 presented with bilateral disease (mean ages: 22.7 and 14.8 months, respectively). Leukocoria was the presenting sign in 56% of patients, leukocoria and strabismus in 18%, strabismus in 13%, inflammation in 8%, and "other"signs in 5%. The fovea was affected by the retinoblastoma tumor or its sequelae in 75% of patients. Patients who presented with strabismus were significantly more likely to have foveal involvement than patients who presented with leukocoria alone (P = .001). Thirty-one percent of patients had strabismus as a component of their presentation; 63% had exotropia, 23% had esotropia, and 14% had variable strabismus. The percentage of patients with strabismus increased to 66% when small angle and variable strabismus were also considered. Patients with inflammation had worse ocular survival (P < .05). Conclusions: This study assessed the combination of leukocoria and strabismus as presenting features of retinoblastoma. Foveal involvement is common in patients who have strabismus and may influence decisionmaking regarding globe salvage. The authors confirmed that exotropia is more common than esotropia in retinoblastoma in the largest cohort to have undergone an orthoptic assessment.