Scarce data exist about clinical/radiological differences between acute ischemic strokes diagnosed in the emergency room (AISER) and stroke chameleons (SC). We aimed at describing the differences observed in a comprehensive stroke center in Chile. Prospective observational study of patients with ischemic stroke syndromes admitted to the ER of Clínica Alemana between December 2014 and October 2023. 1197 patients were included; of these 63 (5.2%, 95%CI 4.1-6.6) were SC; these were younger (p<0.001), less frequently hypertensive (p=0.03) and they also had lower systolic (SBP) (p<0.001), diastolic blood pressures (DBP) (p=0.011), and NIHSS (p<0.001). Clinically they presented less frequently gaze (p=0.008) and campimetry alterations (p=0.03), facial (p<0.001) and limb weakness (left arm (p=0.004), right arm (p=0,041), left leg (p=0.001), right leg P=0.0029), sensory abnormalities (p<0.001), and dysarthria (p<0.001). Neuro-radiological evaluations included less frequently large vessel occlusions (p=0.01), and stroke locations (p=0.005); they also differed in their etiologies (p<0.001). Brainstem strokes (p<0.001) and extinction/inattention symptoms (p<0.001) were only seen in AISER. In multivariate analysis, younger age (OR: 0.945; 95% CI 0.93 - 0.96), DBP (OR: 0.97; 95% CI, 0.95-0.99), facial weakness (OR: 0.39; CI 95% 0.19-0.78), sensory abnormities (OR: 0.16.18; 95% CI, 0.05-0.4), infratentorial location (OR: 0.36; 95% CI, 0.15-0.78), posterior circulation involvement (OR: 3.02; 95% CI, 1.45-6.3), cardioembolic (OR: 3.5; 95% CI, 1.56-7.99) and undetermined (OR: 2.42; 95% CI, 1.22-4.7; 95%) etiologies, remained statistically significant. A stepwise analysis including only clinical elements present on the patient's arrival to the ER, demonstrates that age (OR: 0.95; 95% CI 0.94 - 0.97), DBP (OR: 0.97; 95% CI, 0.95-0.99), the presence of atrial fibrillation (OR: 2.22; 95% CI, 1.04-4.75, NIHSS (OR: 0.88; 95% CI, 0.71-0.89) and the presence in NIHSS of 1.a Level of consciousness (OR: 5.66; CI 95% 1.8-16.9), 1.b Level of consciousness questions (OR: 3.023; 95% CI, 1.35-6.8), facial weakness (OR: 0.3; CI 95% 0.17-0.8) and sensitive abnormalities (OR: 0.27; 95% CI, 0.1-0.72) remained statistically significant. SC had clinical and radiological differences compared to AISER. An additional relevant finding is that any neurological symptom in a patient with atrial fibrillation, even in the presence of a negative DWI should be considered an episode of stroke until this is satisfactorily ruled out.