Ophthalmic specimens range in size and degree of complexity. The diagnostic work-up of ocular-, ophthalmic biopsies and larger specimens demands close collaboration between the clinician, the pathologist and other specialties, including the vitreoretinal surgeon, plastic surgeon, as well as the head-and-neck surgeon. Documentation of all relevant clinical information in the pathology request form as well as timely discussions between the various specialists (e.g., telephone or E-mail communications prior to a biopsy being performed) are essential components of the diagnostic and referral pathways. The laboratory itself should be equipped with experienced technical staff who are dedicated to eye specimens and familiar with the specimen protocols. Further, a pathologist with expertise in ocular pathology/fluid samples should be supported with a wide range of investigations, including molecular diagnostic techniques. In this way, the yield from these samples can be optimized to reach an unequivocal diagnosis, rapid communication to the clinician, and timely instigation of therapy. Guidelines for these steps are provided.