It is important to carefully and urgently evaluate any child with leukocoria for the possibility of retinoblastoma, although fortunately many children referred for this complaint will have a normal examination (i.e., pseudo-leukocoria). Commonly, it is the parents who first notice the abnormal or asymmetric pupil reflex in a photograph. The flash from a camera typically causes the eye to appear red, since the pupil does not have time to contract and the camera captures a red reflection from the normal retina. Any condition that blocks the camera’s flash from reaching the retina may produce a unilateral whitish pupil reflex (i.e., photoleukocoria) [2]. However, it should be kept in mind that photoleukocoria does not always indicate an underlying pathologic condition. There are case series of patients with documented unilateral leukocoria on photographs who had normal ocular examinations [6]. This phenomenon has been termed pseudo-leukocoria since the examination did not reveal any pathology. In these cases, the child appears to be fixating 15° off axis (inward deviation), which likely resulted in an abnormal light reflex off the optic nerve in that eye (Fig. 2.2). Therefore, photoleukocoria is expected to be unilateral (i.e., one eye in a given photo). Alternating photoleukocoria may occur. Simultaneous bilateral photoleukocoria indicates either true leukocoria or esotropia. However, it is critical that any child with possible leukocoria noted by the parents or any health care professional have an urgent eye examination by an experienced pediatric ophthalmologist or ocular oncologist [7].