Under steady‐state conditions the central nervous system (CNS) is traditionally thought to be devoid of antigen presenting cells; however, putative dendritic cells (DCs) expressing enhanced yellow fluorescent protein (eYFP) are present in the retina and brain parenchyma of CD11c‐eYFP mice. We previously showed that these mice carry the Crb1^rd8 mutation, which causes retinal dystrophic lesions; therefore we hypothesized that the presence of CD11c‐eYFP⁺ cells within the CNS may be due to pathology associated with the Crb1^rd8 mutation. We generated CD11c‐eYFP Crb1^wt/wt mice and compared the distribution and immunophenotype of CD11c‐eYFP⁺ cells in CD11c‐eYFP mice with and without the Crb1^rd8 mutation. The number and distribution of CD11c‐eYFP⁺ cells in the CNS was similar between CD11c‐eYFP Crb1^wt/wt and CD11c‐eYFP Crb1^rd8/rd8 mice. CD11c‐eYFP⁺ cells were distributed throughout the inner retina, and clustered in brain regions that receive input from the external environment or lack a blood‐brain barrier. CD11c‐eYFP⁺ cells within the retina and cerebral cortex of CD11c‐eYFP Crb1^wt/wt mice expressed CD11b, F4/80, CD115 and Iba‐1, but not DC or antigen presentation markers, whereas CD11c‐eYFP⁺ cells within the choroid plexus and pia mater expressed CD11c, I‐A/I‐E, CD80, CD86, CD103, DEC205, CD8α and CD135. The immunophenotype of CD11c‐eYFP⁺ cells and microglia within the CNS was similar between CD11c‐eYFP Crb1^wt/wt and CD11c‐eYFP Crb1^rd8/rd8 mice; however, CD11c and I‐A/I‐E expression was significantly increased in CD11c‐eYFP Crb1^rd8/rd8 mice. This study demonstrates that the overwhelming majority of CNS CD11c‐eYFP⁺ cells do not display the phenotype of DCs or their precursors and are most likely a subpopulation of microglia. GLIA 2016. GLIA 2016;64:1331–1349