For individuals born with EB, it can be first recognized at birth or during the first several weeks of life. The most prominent characteristic of EB is that the skin is fragile, which can lead to the development of blisters and wounds in the skin after mild trauma (e.g., injury from a bump or light friction).

The amount of blistering can vary from very little to quite extensive. The blisters are often localized to trauma-prone surfaces of the skin such as the elbows, knees, back of the hands, nails, feet, and toes as well as the diaper area in infants. The mucous membranes may also be involved. Blisters may form in the mouth, larynx and esophagus. There have also been reports of involvement of the eye, which in some reports has caused blindness. These blisters can be very painful and as mentioned previously, can result in scarring.