Human papillomavirus is the ethological agent of various tumors, including plantar warts as one of the most frequent clinical presentations. Diagnosis of these warts continues to be mainly clinical, and a significant incidence of misdiagnosis leads to inadequate treatment. The aim of this study is to implement and validate a multiplex PCR detection method in the clinical setting to detect HPV in samples and to study genotype distribution in Spain to improve future molecular diagnostics. Viral DNA was extracted from 128 samples of clinically suspected plantar warts from various locations in Spain. A multiplex PCR was run alongside internal controls, and amplicons were processed for sequencing and HPV genotyping. The method was validated by assessing both inter- and intra-run repeatability. The PCR detection method returned 81.2 % (n = 104) positive results in the samples tested. Inter- and intra-run repeatability tests showed excellent intra-run agreement (κ = 1.00, p < 0.001) and good inter-run agreement (κ = 0.737, p < 0.001). The most frequent HPV type was HPV1, followed by HPV27, showing a statistical difference between the distribution of HPV genotypes in different areas of Spain. Clinical implementation of a DNA PCR detection method for plantar warts can avoid 18.8 % of unnecessary treatments in doubtful cases, and the method is reliable and validated for the purpose. HPV types show an asymmetric geographical distribution that should be considered for diagnosis and treatment.