Depth of invasion is an important prognostic factor for patients with vulvar squamous cell carcinoma. The aim of this study was to identify the most optimal method of measuring the depth of invasion in relation to the individual outcome in patients with vulvar squamous cell carcinoma. Data of 175 consecutive patients with a primary vulvar squamous cell carcinoma with known lymph node status, treated in the Radboud University Medical Center, the Netherlands (2000-2010), were stored in a database. At pathology review of 148 (85%) cases, depth of invasion was measured using the conventional and alternative methods. Clinical and pathological characteristics of patients with a change in FIGO stage were compared with those without a change in stage. In 148 vulvar squamous cell carcinoma patients, the median depth of invasion was shown to be decreased from 5.5 mm (range 1.1-20) using the conventional method to 3.6 mm (range 0.2-20) using the alternative method (P<0.05). This led to a change in the FIGO stage in 13 of the 148 (9%) patients and a change in depth of invasion from 3.5 to 0.2 mm in one patient (1%) with FIGO stage IIIA. Of all 69 stage 1B patients, 13 (19%) were downstaged to stage IA. The downstaged patients developed less recurrences (15% vs 39%) and had a higher disease-specific survival (100% vs 84%) compared with the patients who remained FIGO stage IB. Using the alternative method for measuring the depth of invasion in tumors of vulvar squamous cell carcinoma patients, 19% of the patients with a FIGO stage IB tumor might be treated without groin surgery resulting in less treatment-related morbidity. The results are promising but more prospective data on a higher number of patients are necessary.