Intravital Microscopy for Identifying Tumor Vessels in Patients With Stage IA-IV Melanoma That is Being Removed by Surgery

Inclusion Criteria:

* Have an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
* Have measurable disease in their skin by direct visualization (visible lesion typically \> 0.5 cm in maximal diameter); to perform a microscopic observation, the lesion will have to be visible by the naked eye, lined-up visually, and be able to interface with the microscope objective; a melanoma lesion that is smaller than 0.5 cm in diameter would present several obstacles to obtaining a reliable microscopic observation in the operating room; therefore, a visible lesion, at a minimum of 0.5 cm in diameter, is proposed for this study
* Melanoma tumor that requires a wide local excision in the operating room; this may include any stage of melanoma from stage IA to stage IV that requires a wide excision in the operating room
* Subject or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
* To determine any sensitivity to fluorescein, subject must have a skin prick test preoperatively (at the time of the preoperative visit and after signed informed consent for entry into this clinical trial is given); a negative skin prick test to fluorescein is an inclusion criteria

Exclusion Criteria:

* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Melanoma deposit is deemed inaccessible to microscopic observation during the operative procedure (i.e., lesion is less than 0.5 cm or is not clearly visible to the naked eye)
* Renal dysfunction as defined as a glomerular filtration rate (GFR) \< 70
* Any known allergy or prior reaction to fluorescein; also, a positive skin prick test to fluorescein is considered an exclusion criteria and the patient would not be eligible for entry into this study
* Pregnant or nursing female subjects
* Unwilling or unable to follow protocol requirements
* Any condition which in the Investigator's opinion deems the subject an unsuitable candidate to undergo observational study (may also include preoperative testing results including electrocardiogram \[EKG\], chest x-ray, or pulmonary function tests that preclude a wide excision in the operating room)