Acute syphilitic posterior placoid chorioretinitis (ASPPC) is a rare clinical manifestation of ocular syphilis. Spontaneous resolution of this condition has been reported in a few cases. The aim of this manuscript is to report an additional case and to discuss the possible pathogenesis of this condition by reviewing the current evidence on this subject. A 45-year-old man presented to us with decreased vision in the right eye secondary to a placoid macular lesion. Fourteen days after presentation, there was a dramatic improvement of the vision, and multimodal retinal imaging showed almost complete spontaneous resolution of the placoid lesion. Syphilis serology turned out positive and a diagnosis of ASPPC was made. The pathogenesis of ASPPC is unclear, and there is contrasting evidence about the role of the cellular immune system. Since this condition may resolve spontaneously before systemic antimicrobial treatment, the presence of a placoid macular lesion should raise a high suspicion of ASPPC in order to make a timely diagnosis and to avoid progression of untreated syphilis.