This case report highlights the usefulness of Ultrasound Biomicroscopy (UBM) in a case of retinoblastoma which showed massive anterior chamber involvement after treatment with intra-arterial chemotherapy. UBM was used to document tumour pseudohypopion, cells in the aqueous humor, implanted clusters of cells on the corneal endothelium, iris nodules, lens capsule deposits and ciliary body invasion. The UBM data, compared with the histopathologic analysis, performed on eye tissue, after enucleation of the affected eye, revealed a significant concordance. UBM may represent an important diagnostic tool in retinoblastoma, when the decision about enucleation of the eye must be made in the absence of histopathologic data.