Due to a multitude of factors, skin cancer incidence is increasing and challenges medical professionals in biopsy decision-making. While skin cancer may have a profound impact on the patient and be costly for society, there is little knowledge about the number and cost of benign skin lesions biopsied as collateral damage. This study evaluates the number and costs of skin biopsies in Denmark over 15 years, focusing on benign and malignant skin lesions and melanomas across medical settings. It aims to determine the benign to malignant ratio (BMR) and number needed to biopsy (NNB) and estimate the direct cost of benign skin lesion biopsies in the Cancer Pathway from the perspective of a public healthcare system. The study included 4,481,207 biopsy specimens from January 2007 to June 2022 from the Danish Pathology Data Bank, of which 151,988 from the Cancer Pathway were included in the primary analysis of BMR. The national reimbursement rates for biopsies were used, alongside histopathological examination costs extracted from several pathology departments, for a Monte-Carlo simulation of a simple cost and sensitivity analysis. The number of biopsies increased by 39.1% from 2007 to 2021. Overall BMR for malignancy was 4.1:1, and NNB for melanoma was 31.8, but biopsies performed on clinical suspicion of malignancy or melanoma had a BMR and NNB of 1.5:1 and 2.8, respectively. The cost of benign skin biopsies performed on suspicion of cancer or melanoma in 2021 was €6.6M, predominantly in hospitals. A healthcare system that employs filtering functions before biopsy of skin lesions can achieve some of the lowest BMR reported in the world, but with most benign skin lesion excisions due to suspicion of malignancy performed in the expensive hospital setting. Including clinical reason for biopsy in diagnostic accuracy studies using NNB is crucial.