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Simple Summary: The pathological status of regional lymph nodes (pN) is the most important predictor of survival in patients with invasive squamous cell carcinoma of the penis. However, staging strategies have limited prediction, which results in false-negative findings or unnecessary lymphadenectomies. Therefore, additional criteria should be identified to improve the prediction of lymph node involvement. The "Cellular Dissociation Grade" (CDG) is based on tumor cell budding and cell nest size. Many studies have examined the CDG in squamous cell carcinomas of other organs such as the lungs, oral cavity, pharynx, larynx, cervix and esophagus. In this study, the CDG was examined in 109 cases of invasive penile squamous cell carcinoma that were treated at the University Medicine Rostock between 2014 and 2022. Furthermore, its correlation with the pathologic status of regional lymph nodes (pN) as the main prognostic factor was verified. Finally, cellular dissociation grading was compared with classic WHO grading. The results showed that pN in penile squamous cell carcinoma showed a highly significant association with the CDG and no statistically significant association with WHO grading. These results support the notion that cellular dissociation grading is an important prognostic factor for squamous cell carcinoma. [ABSTRACT FROM AUTHOR]