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Simple Summary: Tumor budding (TB), poorly differentiated clusters (PDCs), and the Stroma AReactive Invasion Front Area (SARIFA) are emerging biomarkers offering fast and cost-effective ways of assisting the clinical therapeutic decision. However, in esophageal cancers, their applicability has not been fully elucidated. In our retrospective study, we examined these invasion markers in a cohort of esophageal squamous cell cancers and adenocarcinomas, with a special focus on lymphatic spread. According to our results, different invasive patterns are prognostic in histological subtypes of esophageal cancer, namely, SARIFA in adenocarcinomas and TB in squamous cell carcinomas. However, only in squamous cell cancers were TB and PDC useful for the prediction of overall survival. In adenocarcinomas, neither of the aforementioned markers were significant regarding survival prediction, possibly due to the small cohort size. Both esophageal squamous cell carcinoma (ESQCC) and adenocarcinoma (EAC) are known to have poor prognosis. We aimed to investigate the invasion front areas of 57 ESQCC and 43 EAC cases to find histological signs of metastatic progression. Tumor cell clusters with different cell counts, including tumor buds (TBs) and poorly differentiated clusters (PDCs), were assessed. The presence of the recently described Stroma AReactive Invasion Front Area (SARIFA) phenomenon, which defines a direct contact between tumor cells and adipocytes, was more frequently observed in EAC than in ESQCC (p = 0.004). In adenocarcinomas, a higher prevalence of SARIFA was observed in tumors with a higher number of small clusters (TBs and small PDCs; p < 0.001); furthermore, both the high number of TBs (p = 0.016) and the presence of SARIFA (p = 0.001) correlated with a higher pT stage. SARIFA positivity in EAC (p = 0.011) and high TB in ESQCC (p = 0.0006) were found to be independent prognostic factors for lymph node metastases. Moreover, in ESQCC, the higher absolute number of both TBs and PDCs was associated with shorter overall survival (p = 0.0269 and p = 0.0377, respectively). Our results suggest that the histological subtypes of esophageal cancer behave differently, namely, that different features of the invasion front are of prognostic significance. [ABSTRACT FROM AUTHOR]