Retinoblastoma can present in a variety of ways. The majority of retinoblastoma patients present with a white pupil reflex or leukocoria instead of a normal healthy black pupil or red reflex similar to the one seen when photographs are taken of a child looking directly into the camera. This abnormal white pupillary reflex is sometimes referred to as a cat's eye reflex.

Many times the parent is the first one to notice the cat's eye reflex. Other eye diseases can also present with this white pupillary reflex; leukocoria does not always indicate retinoblastoma. An ophthalmologist can determine the correct diagnosis.

A crossed eye or strabismus is the second most common manner in which retinoblastoma presents. The child's eye may turn out (towards the ear), called exotropia, or turn in (towards the nose), called esotropia.

Retinoblastoma may also present with a red, painful eye, poor vision, inflammation of tissue surrounding the eye, an enlarged or dilated pupil, different colored irides (heterochromia), failure to thrive (trouble eating or drinking), extra fingers or toes, malformed ears, or retardation. On rare occasions, retinoblastoma is discovered on a well-baby examination. Most often, the symptoms of retinoblastoma are first detected by a parent.