This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Skin biopsy is an established method for allying the dermatologist in overcoming the diagnostic dilemmas which occur during consultations. However neither do all skin biopsies produce a conclusive diagnosis nor the dermatologists routinely perform this procedure to every patient they consult. The aim of this study was to investigate the favourable clinical diagnoses set by dermatologists when performing skin biopsy, the diagnoses reached by the dermatopathologists after microscopic examination, and the relationship between them and finally to comment on the instances that skin biopsy fails to fulfill the diagnostic task. Methods. Six thousand eight hundred and sixteen biopsy specimens were reviewed and descriptive statistics were performed. Results. The mean age of the patients was 54.58 ± 0.26 years, the most common site of biopsy was the head and neck (38.3%), the most frequently proposed clinical diagnoses included malignancies (19.28%), and the most prevalent pathological diagnosis was epitheliomas (21.9%). After microscopic examination, a specific histological diagnosis was proposed in 83.29% of the cases and a consensus between clinical and histological diagnoses was observed in 68% of them. Conclusions. Although there are cases that skin biopsy exhibits diagnostic inefficiency, it remains a valuable aid for the dermatology clinical practice. 1. Introduction The management of skin diseases requires a pertinent diagnosis, which in many occasions constitutes an intricate process. Skin biopsy is an established diagnostic procedure which connects clinical diagnostic methodology with the invisible to the unaided eye microscopic field of skin pathology. Taking under consideration the potentials and limitations of optical microscopy and the indications of performing an invasive technique, dermatologists often rely on skin biopsy for enhancing their diagnostic abilities. The aim of this study was to investigate the favourable clinical diagnoses set by dermatologists when performing skin biopsy, the diagnoses reached by the dermatopathologists after microscopic examination, as well as the relationship between them, and finally to comment on the instances that skin biopsy fails to fulfill the diagnostic task. 2. Methods Six thousand eight hundred and sixteen (6816) biopsies were reviewed which were included in 5941 histopathology report forms and were processed in the “Andreas Sygros” hospital during the years 2004–2006. Furthermore, a topographic anatomy coding system was developed along with an ad hoc coding system for skin diseases in order to meet the requirements of the study (data not shown). Each of the 5941 patients underwent at least one and at most seven skin biopsies at any session. The frequencies of the various sites of biopsy, the percentages of all clinical diagnoses proposed by the dermatologists, and the percentages of the histological diagnoses set by the dermatopathologists were calculated and statistical significance was evaluated. Data were analyzed using PASW Statistics version 18 (SPSS Inc, Chicago IL). Descriptive statistics were applied Hindawi Publishing Corporation Dermatology Research and Practice Volume 2014, Article ID 734906, 5 pages http://dx.doi.org/10.1155/2014/734906 2 Dermatology Research and Practice including frequencies and percentages, as well as the chisquare test, both for one-way and contingency tables. The level of significance was set at less than 0.05. 3. Results 3.1. Gender and Age. Out of 5941 patients that underwent skin biopsy, 48.2% (𝑛 = 2862) were males and 51.8% (𝑛 = 3075) females, with 𝑛=4 missing data. The mean age was 54.58 ± 0.26 and the median 57 years. The mean age for males was 56.54±0.37 (median 60 years) and for females 52.79±0.36 (median 54 years). 3.2. Site of Biopsy. The site of each biopsy was studied regarding both anatomic regions and specific locations. Regarding anatomic regions, the respective frequencies were found to be the hea