Retinoblastoma is the most common intraocular malignancy in infancy and childhood. The incidence varies in different populations. Mutations of the retinoblastoma susceptibility gene have been implicated in malignant retinoblastoma. This research seeks to identify any mutations that could be present in exon 19 and have implications in the pathogenesis of retinoblastoma among children in Calabar. Children (9) with retinoblastoma attending the University of Calabar teaching Hospital (UCTH), Dept of Opthalmology. 30 unrelated and unmatched controls with no history of retinoblastoma were recruited into the study. 2- 3mls of blood was collected from each child, genomic DNA was extracted from blood, PCRs and sequencing were performed on exon 19. The nucleotide sequences of the RB1 gene were decoded from the chromatogram using Bioedit software and aligned manually. Multiple sequence alignment was performed using CLUSTAL W. The RB1 gene mutation frequencies were 2(22.2%) and 3(33.3%) for missense mutations and deletions respectively. Sequencing revealed two missense mutations namely: g.98A>G (p.Y33C) and g.154A>G (p.I52V) in a male patient and a female patient. Deletions include: g.1delC, g.1-12delCAGGAAAACCA, g.45-46delAA, g.14- 21delTTATTAAA and g.1-55delCAGGAA…..TTC were all observed in male (bilateral) cases of retinoblastoma 3(11.1%). These mutations were absent in 6(66.6%) children and the control subjects. Two missense and five deletions were observed in four males and a female patient. The RB1 gene mutation frequency was low among the retinoblastoma children, implying that these mutations were not directly responsible for retinoblastoma, the main causal mutation may be present in other exons. Exon 19 needs to be investigated in a larger population.