While solitary chancres are the rule, multiple chancres are common, especially in those who are HIV-infected. While the genital areas and oropharynx are the most common sites to find syphilitic chancres, they may occur anywhere that Treponema pallidum has been inoculated. Inquiry into sexual practices is essential when evaluating lesions as possible primary syphilis.

It is very important to remember that atypical lesions may occur in as many as 60% of cases. On occasion, primary syphilis may occur without a primary lesion present, or with a lesion so atypical it is never considered as syphilitic.

Regional lymphadenopathy accompanies chancres; beginning unilaterally, it may become bilateral if treatment is delayed. The nodes are discrete, rubbery, nontender, and nonerythematous.